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1950a Psychopharmacology Part 2 of 2
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Grand Rounds presentation given at Naval Medical Center Portsmouth Department of Psychiatry in 2006 covering psychopharmacological advances of the 1950s with an emphasis on iproniazid, imipramine and meprobamate. Part II of II.
By:
Kevin
10 months 18 days ago
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Presentation Transcript
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| Slide 1 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO | | Slide 2 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO | | Slide 3 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? | | Slide 4 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? | | Slide 5 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 | | Slide 6 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford | | Slide 7 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford | | Slide 8 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 | | Slide 9 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? | | Slide 10 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? | | Slide 11 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. | | Slide 12 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? | | Slide 13 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST | | Slide 14 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. | | Slide 15 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods | | Slide 16 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy | | Slide 17 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods | | Slide 18 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy | | Slide 19 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… | | Slide 20 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES | | Slide 21 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… | | Slide 22 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… | | Slide 23 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) | | Slide 24 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? | | Slide 25 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 | | Slide 26 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 Example: diphenhydramine Aryl groups at R3 & R4 Methyl groups at R1 & R2 X = oxygen | | Slide 27 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 Example: diphenhydramine Aryl groups at R3 & R4 Methyl groups at R1 & R2 X = oxygen henri laborit Experimented with various phenothiazine anti-histamines in his lytic cocktails to reduce analgesia required in effort to reduce surgical shock | | Slide 28 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 Example: diphenhydramine Aryl groups at R3 & R4 Methyl groups at R1 & R2 X = oxygen henri laborit Experimented with various phenothiazine anti-histamines in his lytic cocktails to reduce analgesia required in effort to reduce surgical shock paul charpentier Charpentier synthesized a series of phenothiazines that were strongly antihistaminergic.
The most prominent of these was promethazine Rhône-Poulenc chemist
phenothiazine expert
synthesized the first tricyclic antihistamine, promethazine | | Slide 29 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 Example: diphenhydramine Aryl groups at R3 & R4 Methyl groups at R1 & R2 X = oxygen henri laborit Experimented with various phenothiazine anti-histamines in his lytic cocktails to reduce analgesia required in effort to reduce surgical shock paul charpentier Charpentier synthesized a series of phenothiazines that were strongly antihistaminergic.
The most prominent of these was promethazine Rhône-Poulenc chemist
phenothiazine expert
synthesized the first tricyclic antihistamine, promethazine Promethazine fits the classic structure of an antihistamine | | Slide 30 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 Example: diphenhydramine Aryl groups at R3 & R4 Methyl groups at R1 & R2 X = oxygen henri laborit Experimented with various phenothiazine anti-histamines in his lytic cocktails to reduce analgesia required in effort to reduce surgical shock paul charpentier Charpentier synthesized a series of phenothiazines that were strongly antihistaminergic.
The most prominent of these was promethazine Rhône-Poulenc chemist
phenothiazine expert
synthesized the first tricyclic antihistamine, promethazine Promethazine fits the classic structure of an antihistamine Flight Plan for Anesthetic Objective
“…like a conscientious airman [the anesthesiologist] previously has filed a flight plan that, when carefully followed, leads to the objective…”
To relieve apprehension
To produce light sleep
To reduce the incidence of nausea and vomiting | | Slide 31 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 Example: diphenhydramine Aryl groups at R3 & R4 Methyl groups at R1 & R2 X = oxygen henri laborit Experimented with various phenothiazine anti-histamines in his lytic cocktails to reduce analgesia required in effort to reduce surgical shock paul charpentier Charpentier synthesized a series of phenothiazines that were strongly antihistaminergic.
The most prominent of these was promethazine Rhône-Poulenc chemist
phenothiazine expert
synthesized the first tricyclic antihistamine, promethazine Promethazine fits the classic structure of an antihistamine Flight Plan for Anesthetic Objective
“…like a conscientious airman [the anesthesiologist] previously has filed a flight plan that, when carefully followed, leads to the objective…”
To relieve apprehension
To produce light sleep
To reduce the incidence of nausea and vomiting Laborit wonders if there’s an even better compound than promethazine for his "lytic cocktail" Patients given promethazine were more calmer after surgery,
needed less
post-op morphine and
anesthesia | | Slide 32 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 Example: diphenhydramine Aryl groups at R3 & R4 Methyl groups at R1 & R2 X = oxygen henri laborit Experimented with various phenothiazine anti-histamines in his lytic cocktails to reduce analgesia required in effort to reduce surgical shock paul charpentier Charpentier synthesized a series of phenothiazines that were strongly antihistaminergic.
The most prominent of these was promethazine Rhône-Poulenc chemist
phenothiazine expert
synthesized the first tricyclic antihistamine, promethazine Promethazine fits the classic structure of an antihistamine Flight Plan for Anesthetic Objective
“…like a conscientious airman [the anesthesiologist] previously has filed a flight plan that, when carefully followed, leads to the objective…”
To relieve apprehension
To produce light sleep
To reduce the incidence of nausea and vomiting Laborit wonders if there’s an even better compound than promethazine for his "lytic cocktail" Patients given promethazine were more calmer after surgery,
needed less
post-op morphine and
anesthesia henri laborit Laborit asks
Rhône-Poulenc to make a more centrally-acting antihistamine | | Slide 33 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 Example: diphenhydramine Aryl groups at R3 & R4 Methyl groups at R1 & R2 X = oxygen henri laborit Experimented with various phenothiazine anti-histamines in his lytic cocktails to reduce analgesia required in effort to reduce surgical shock paul charpentier Charpentier synthesized a series of phenothiazines that were strongly antihistaminergic.
The most prominent of these was promethazine Rhône-Poulenc chemist
phenothiazine expert
synthesized the first tricyclic antihistamine, promethazine Promethazine fits the classic structure of an antihistamine Flight Plan for Anesthetic Objective
“…like a conscientious airman [the anesthesiologist] previously has filed a flight plan that, when carefully followed, leads to the objective…”
To relieve apprehension
To produce light sleep
To reduce the incidence of nausea and vomiting Laborit wonders if there’s an even better compound than promethazine for his "lytic cocktail" Patients given promethazine were more calmer after surgery,
needed less
post-op morphine and
anesthesia henri laborit Laborit asks
Rhône-Poulenc to make a more centrally-acting antihistamine PROMAZINE Replaced isopropyl group with a straight carbon chain propyl propyl
(3-carbon alkyl) | | Slide 34 : Psychopharmacologic Advances 1950-60 Part 2: Iproniazid,
Imipramine and Meprobamate Kevin Nasky, DO Not much. WHAT DID WE KNOW IN 1950? Brain was thought to be entirely electrical
Acetylcholine was the only known neurotransmitter
Knew acetylcholine was inactivated by choline esterase WHAT DID WE KNOW IN 1950? Existence of serotonin in platelets
LSD (that it was a hallucinogen and that it was chemically related to 5HT)
The enzyme that oxidized adrenaline: “Amine Oxidase”
Antihistamines DISCOVERED BEFORE 1950 “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford “When I was an undergraduate student at Cambridge (late 50s) we were taught…there was no chemical transmission in the brain… Neurotransmission was thought to be an entirely electrical phenomena 1950 that it was just an electrical machine”
Pharmacologist Leslie Iverson, Professor emeritus, U. of Oxford Acetylcholine was known to be a neurotransmitter, but in the peripheral nervous system only 1950 A lot. WHAT DIDN’T WE KNOW IN 1950? For example… WHAT DIDN’T WE KNOW IN 1950? …as late as 1960, (now Nobel laureate) Arvid Carlsson was practically laughed out of town when he proposed that dopamine might be a neurotransmitter. Since neurotransmitters were not even understood to play any role in the CNS, there was virtually no basis to understand the astounding clinical findings revealed in the decade ahead. WHAT DIDN’T WE KNOW IN 1950? THE CONCEPT OF AN ANTIPSYCHOTIC OR AN ANTIDEPRESSANT DID NOT EXIST HOW WERE WE TREATING MENTAL ILLNESS IN 1950? Most “treatments” were simply measures to sedate patients in overcrowded asylums. Physical Methods Insulin coma ECT Leucotomy Bromides Barbiturates
Paraldehyde Opioids Psychotropic Methods Psychosis
Depression
Anxiety TREATMENTS OF CHOICE Insulin Coma
Deep Sleep
ECT
Opioids
Various meds
Leukotomy Chlorpromazine and Reserpine A QUICK REVIEW… Chlorpromazine IN SEARCH OF BETTER ANTIHISTAMINES What do Benadryl, Phenergan,
Thorazine and Tofranil have in common? Speaking of Antihistamines… Definitely not their indications:
allergies, nausea,
psychosis and depression, respectively. Speaking of Antihistamines… A (very) short course in the chemistry of antihistamines: How Benadryl became Thorazine (well, sort of) Simple.
4 Easy Steps… HOW DO YOU MAKE AN ANTIHISTAMINE? Start with a substituted ethyl amine Substitute methyl or other short alkyl groups in R1 and R2
X = C, O or N
Add an aryl group at R3 and R4 Example: diphenhydramine Aryl groups at R3 & R4 Methyl groups at R1 & R2 X = oxygen henri laborit Experimented with various phenothiazine anti-histamines in his lytic cocktails to reduce analgesia required in effort to reduce surgical shock paul charpentier Charpentier synthesized a series of phenothiazines that were strongly antihistaminergic.
The most prominent of these was promethazine Rhône-Poulenc chemist
phenothiazine expert
synthesized the first tricyclic antihistamine, promethazine Promethazine fits the classic structure of an antihistamine Flight Plan for Anesthetic Objective
“…like a conscientious airman [the anesthesiologist] previously has filed a flight plan that, when carefully followed, leads to the objective…”
To relieve apprehension
To produce light sleep
To reduce the incidence of nausea and vomiting Laborit wonders if there’s an even better compound than |
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