Benzodiazepines: Difference between revisions

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.  

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>

The new group of drugs was initially greeted with optimism by the medical profession, but gradually concerns arose; in particular, the risk of dependence became evident in the 1980s. Benzodiazepines have a unique history in that they were responsible for the largest-ever class-action lawsuit against drug manufacturers in the United Kingdom, involving 14,000 patients and 1,800 law firms that alleged the manufacturers knew of the dependence potential but intentionally withheld this information from doctors.  

Although antidepressants with anxiolytic properties have been introduced, and there is increasing awareness of the adverse effects of benzodiazepines, prescriptions for short-term anxiety relief have not significantly dropped.<ref name="pmid18671662">{{cite journal | author = Lader M | title = Effectiveness of benzodiazepines: do they work or not? | journal = Expert Rev Neurother | volume = 8 | issue = 8 | pages = 1189–91 | year = 2008 | pmid = 18671662 | doi = 10.1586/14737175.8.8.1189 | type =  PDF }}</ref> For treatment of insomnia, benzodiazepines are now less popular than nonbenzodiazepines, which include [[zolpidem]], zaleplon and [[zopiclone|eszopiclone]].<ref>{{cite journal | author = Jufe GS | title = [New hypnotics: perspectives from sleep physiology] | journal = Vertex | volume = 18 | issue = 74 | pages = 294–9 | date = Jul–Aug 2007 | pmid = 18265473 }}</ref> Nonbenzodiazepines are molecularly distinct, but nonetheless, they work on the same benzodiazepine receptors and produce similar sedative effects.<ref name="wake">{{cite journal | author = Lemmer B | title = The sleep–wake cycle and sleeping pills | journal = Physiol Behav | volume = 90 | issue = 2–3 | pages = 285–93 | year = 2007 | pmid = 17049955 | doi = 10.1016/j.physbeh.2006.09.006 }}</ref>

Paradoxical reactions to [[benzodiazepines]] such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).<ref>http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review</ref><ref>Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf</ref><p>

}}

Benzodiazepines are known to be [[Addiction potential::extremely physically and psychologically addictive]].{{citation needed}}

===Overdose===