Benzodiazepines: Difference between revisions

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[[File:Chlordiazepoxide.svg|thumb|250px|right|alt=Chemical structure diagram of a benzene ring fused to a diazepine ring. Cl is attached to the benzene; N, H, CH3, and O are attached to the diazepine.|The molecular structure of chlordiazepoxide, the first benzodiazepine. It was marketed by Hoffmann–La Roche from 1960 branded as ''Librium''.]]

The first benzodiazepine, chlordiazepoxide (''Librium''), was synthesized in 1955 by Leo Sternbach while working at Hoffmann–La Roche on the development of tranquilizers. The ~~pharmacoogical~~ properties of the compounds prepared initially were disappointing, and Sternbach abandoned the project.

The first benzodiazepine, chlordiazepoxide (''Librium''), was synthesized in 1955 by Leo Sternbach while working at Hoffmann–La Roche on the development of tranquilizers. The pharmacological properties of the compounds prepared initially were disappointing, and Sternbach abandoned the project.

Two years later, on April 1957, co-worker Earl Reeder noticed a "nicely crystalline" compound leftover from the discontinued project while spring-cleaning in the lab. This compound, later named chlordiazepoxide, had not been tested in 1955 because of Sternbach's focus on other issues. Expecting pharmacology results to be negative, and hoping to publish the chemistry-related findings, researchers submitted it for a standard battery of animal tests.

However, the compound showed very strong [[sedative]], [[anticonvulsant]], and [[muscle relaxant]] effects. These impressive clinical findings led to its speedy introduction throughout the world in 1960 under the brand name ''Librium~~'' and specifically in Soviet Union as ''Elenium~~''.<ref name="pmid34039">{{cite journal | author = Sternbach LH | title = The benzodiazepine story | journal = Journal of Medicinal Chemistry | volume = 22 | issue = 1 | pages = 1–7 | year = 1979 | pmid = 34039 | doi = 10.1021/jm00187a001 | quote = During this cleanup operation, my co-worker, Earl Reeder, drew my attention to a few hundred milligrams of two products, a nicely crystalline base and its hydrochloride. Both the base, which had been prepared by treating the quinazoline N-oxide 11 with methylamine, and its hydrochloride had been made sometime in 1955. The products were not submitted for pharmacological testing at that time because of our involvement with other problems }}</ref><ref name="Miller-Gold">{{cite journal |vauthors=Miller NS, Gold MS | title = Benzodiazepines: reconsidered | journal = Adv Alcohol Subst Abuse | volume = 8 | issue = 3–4 | pages = 67–84 | year = 1990 | pmid = 1971487 | doi = 10.1300/J251v08n03_06 }}</ref> Following chlordiazepoxide, [[diazepam]] marketed by Hoffmann–La Roche under the brand name ''Valium'' in 1963, and for a while the two were the most commercially successful drugs. The introduction of benzodiazepines led to a decrease in the prescription of [[barbiturate]]s, and by the 1970s they had largely replaced the older drugs for sedative and [[hypnotic]] uses.<ref name="isbn0-19-517668-5">{{cite book |author=Shorter E |title=A Historical Dictionary of Psychiatry |publisher=Oxford University Press |year=2005 |chapter=Benzodiazepines |pages=41–2 |isbn=0-19-517668-5 }}</ref>

However, the compound showed very strong [[sedative]], [[anticonvulsant]], and [[muscle relaxant]] effects. These impressive clinical findings led to its speedy introduction throughout the world in 1960 under the brand name ''Librium''.<ref name="pmid34039">{{cite journal | author = Sternbach LH | title = The benzodiazepine story | journal = Journal of Medicinal Chemistry | volume = 22 | issue = 1 | pages = 1–7 | year = 1979 | pmid = 34039 | doi = 10.1021/jm00187a001 | quote = During this cleanup operation, my co-worker, Earl Reeder, drew my attention to a few hundred milligrams of two products, a nicely crystalline base and its hydrochloride. Both the base, which had been prepared by treating the quinazoline N-oxide 11 with methylamine, and its hydrochloride had been made sometime in 1955. The products were not submitted for pharmacological testing at that time because of our involvement with other problems }}</ref><ref name="Miller-Gold">{{cite journal |vauthors=Miller NS, Gold MS | title = Benzodiazepines: reconsidered | journal = Adv Alcohol Subst Abuse | volume = 8 | issue = 3–4 | pages = 67–84 | year = 1990 | pmid = 1971487 | doi = 10.1300/J251v08n03_06 }}</ref> Following chlordiazepoxide, [[diazepam]] marketed by Hoffmann–La Roche under the brand name ''Valium'' in 1963, and for a while the two were the most commercially successful drugs. The introduction of benzodiazepines led to a decrease in the prescription of [[barbiturate]]s, and by the 1970s they had largely replaced the older drugs for sedative and [[hypnotic]] uses.<ref name="isbn0-19-517668-5">{{cite book |author=Shorter E |title=A Historical Dictionary of Psychiatry |publisher=Oxford University Press |year=2005 |chapter=Benzodiazepines |pages=41–2 |isbn=0-19-517668-5 }}</ref>

==Society and culture==

@@ Line 11: / Line 11: @@
 [[File:Chlordiazepoxide.svg|thumb|250px|right|alt=Chemical structure diagram of a benzene ring fused to a diazepine ring. Cl is attached to the benzene; N, H, CH3, and O are attached to the diazepine.|The molecular structure of chlordiazepoxide, the first benzodiazepine. It was marketed by Hoffmann–La Roche from 1960 branded as ''Librium''.]]
-The first benzodiazepine, chlordiazepoxide (''Librium''), was synthesized in 1955 by Leo Sternbach while working at Hoffmann–La Roche on the development of tranquilizers. The pharmacoogical properties of the compounds prepared initially were disappointing, and Sternbach abandoned the project.
+The first benzodiazepine, chlordiazepoxide (''Librium''), was synthesized in 1955 by Leo Sternbach while working at Hoffmann–La Roche on the development of tranquilizers. The pharmacological properties of the compounds prepared initially were disappointing, and Sternbach abandoned the project.
 Two years later, on April 1957, co-worker Earl Reeder noticed a "nicely crystalline" compound leftover from the discontinued project while spring-cleaning in the lab. This compound, later named chlordiazepoxide, had not been tested in 1955 because of Sternbach's focus on other issues. Expecting pharmacology results to be negative, and hoping to publish the chemistry-related findings, researchers submitted it for a standard battery of animal tests.
-However, the compound showed very strong [[sedative]], [[anticonvulsant]], and [[muscle relaxant]] effects. These impressive clinical findings led to its speedy introduction throughout the world in 1960 under the brand name ''Librium'' and specifically in Soviet Union as ''Elenium''.<ref name="pmid34039">{{cite journal | author = Sternbach LH | title = The benzodiazepine story | journal = Journal of Medicinal Chemistry | volume = 22 | issue = 1 | pages = 1–7 | year = 1979 | pmid = 34039 | doi = 10.1021/jm00187a001 | quote = During this cleanup operation, my co-worker, Earl Reeder, drew my attention to a few hundred milligrams of two products, a nicely crystalline base and its hydrochloride. Both the base, which had been prepared by treating the quinazoline N-oxide 11 with methylamine, and its hydrochloride had been made sometime in 1955. The products were not submitted for pharmacological testing at that time because of our involvement with other problems }}</ref><ref name="Miller-Gold">{{cite journal |vauthors=Miller NS, Gold MS | title = Benzodiazepines: reconsidered | journal = Adv Alcohol Subst Abuse | volume = 8 | issue = 3–4 | pages = 67–84 | year = 1990 | pmid = 1971487 | doi = 10.1300/J251v08n03_06 }}</ref> Following chlordiazepoxide, [[diazepam]] marketed by Hoffmann–La Roche under the brand name ''Valium'' in 1963, and for a while the two were the most commercially successful drugs. The introduction of benzodiazepines led to a decrease in the prescription of [[barbiturate]]s, and by the 1970s they had largely replaced the older drugs for sedative and [[hypnotic]] uses.<ref name="isbn0-19-517668-5">{{cite book |author=Shorter E |title=A Historical Dictionary of Psychiatry |publisher=Oxford University Press |year=2005 |chapter=Benzodiazepines |pages=41–2 |isbn=0-19-517668-5 }}</ref>
+However, the compound showed very strong [[sedative]], [[anticonvulsant]], and [[muscle relaxant]] effects. These impressive clinical findings led to its speedy introduction throughout the world in 1960 under the brand name ''Librium''.<ref name="pmid34039">{{cite journal | author = Sternbach LH | title = The benzodiazepine story | journal = Journal of Medicinal Chemistry | volume = 22 | issue = 1 | pages = 1–7 | year = 1979 | pmid = 34039 | doi = 10.1021/jm00187a001 | quote = During this cleanup operation, my co-worker, Earl Reeder, drew my attention to a few hundred milligrams of two products, a nicely crystalline base and its hydrochloride. Both the base, which had been prepared by treating the quinazoline N-oxide 11 with methylamine, and its hydrochloride had been made sometime in 1955. The products were not submitted for pharmacological testing at that time because of our involvement with other problems }}</ref><ref name="Miller-Gold">{{cite journal |vauthors=Miller NS, Gold MS | title = Benzodiazepines: reconsidered | journal = Adv Alcohol Subst Abuse | volume = 8 | issue = 3–4 | pages = 67–84 | year = 1990 | pmid = 1971487 | doi = 10.1300/J251v08n03_06 }}</ref> Following chlordiazepoxide, [[diazepam]] marketed by Hoffmann–La Roche under the brand name ''Valium'' in 1963, and for a while the two were the most commercially successful drugs. The introduction of benzodiazepines led to a decrease in the prescription of [[barbiturate]]s, and by the 1970s they had largely replaced the older drugs for sedative and [[hypnotic]] uses.<ref name="isbn0-19-517668-5">{{cite book |author=Shorter E |title=A Historical Dictionary of Psychiatry |publisher=Oxford University Press |year=2005 |chapter=Benzodiazepines |pages=41–2 |isbn=0-19-517668-5 }}</ref>
 ==Society and culture==