Category:Benzodiazepines

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Benzodiazepines are a class of gabaminergic psychoactive chemicals used in the treatment of anxiety and sleep disorders. This class includes alprazolam (Xanax), diazepam (Valium), clonazepam (Klonopin) and others. Most benzodiazepine names end in "pam" or "am".

History

The first benzodiazepine, chlordiazepoxide (Librium) was discovered serendipitously in 1954 by the Austrian scientist Leo Sternbach (1908–2005), working for the pharmaceutical company Hoffmann–La Roche. Chlordiazepoxide was synthesised by accident while trying to synthesise a chemical dye. The chemical class synthesised was initially believed to be heptoxdiazines but on further investigation Leo Sternbach soon discovered the new compound was in fact quinazolone-3-oxides. Leo Sternbach had synthesised 40 derivatives of the quinazolone-3-oxides and tested 39 of them with disappointing results. Leo Sternbach discontinued his work on the remaining compound Ro-5-0690, but he "rediscovered" it in 1957 when an assistant was cleaning up the laboratory. Although initially discouraged by his employer, Sternbach conducted further research that revealed the compound was a very effective tranquilizer. Tests revealed that the compound had hypnotic, anxiolytic, anticonvulsant, and muscle relaxant effects. Three years later chlordiazepoxide was marketed as a therapeutic benzodiazepine medication under the brand name Librium. Following chlordiazepoxide, in 1963 diazepam hit the market under the brand name Valium, followed by oxazepam (Serax) and nitrazepam (Mogadon) in 1965, clorazepate (Tranxene) in 1968, lorazepam (Ativan) in 1973, bromazepam (Lexotan) in 1974, clobazam (Frisium) in 1975, and flunitrazepam (Rohypnol) in 1978.

Dr. Carl F. Essig of the Addiction Research Center of the National Institute of Mental Health spoke at a symposium on drug abuse at an annual meeting of the American Association for the Advancement of Science, in December 1963. He named meprobamate, glutethimide, ethinamate, ethchlorvynol, methyprylon, and chlordiazepoxide as drugs whose usefulness can hardly be questioned. However, Essig labeled these newer products as drugs of addiction, like barbiturates, whose habit-forming qualities were more widely known. He mentioned a 90-day study of chlordiazepoxide, which concluded that the automobile accident rate among 68 users was 10 times higher than normal. Participants' daily dosage ranged from 5 to 100 milligrams.

A related class of drugs that also work on the benzodiazepine receptors, the nonbenzodiazepines, has recently been introduced. Nonbenzodiazepines are molecularly distinct from benzodiazepines and have similar risks and benefits to those of benzodiazepines. There have been suggestions that they may have a better side effect profile with less dependence potential. However, this is controversial and disputed by bodies such as the National Institute for Clinical Excellence.

Effects of Benzodiazepines

Therapeutic uses of benzodiazepines include treatment of anxiety, insomnia (by causing drowsiness), seizures (by increasing the seizure threshold), muscle spasms, and alcohol withdrawal. Side effects caused by benzodiazepines may include drowsiness, dizziness, upset stomach, blurred vision, headache, confusion, depression, euphoria, impaired coordination, changes in heart rate, trembling, weakness, amnesia, grogginess, dreaming or nightmares, chest pain, vision changes, jaundice, and paradoxical reactions. Benzodiazeines are relatively rapid acting and therefore can be used short-term, intermittently, and as needed. This rapid-acting property is useful in the treatment of anxiety which can vary in intensity and for the treatment of acute panic attacks. Rapid cessation of use can not only result in a return of any treated symptoms, but a compensatory increase reaction resulting in greater than normal symptoms. Rapid cessation can also cause symptoms to appear in subjects who previously had no such symptoms. Some effects resulting from cessation of benzodiazepine use may include insomnia, convulsions and seizures, hyper activity, anxiety, and even delirium tremens in severe cases. Benzodiazepines are commonly divided into three different groups depending on the length of the half-life (the time required for half of the drug to be metabolized to an inactive form). The short-acting benzodiazepines have half-lives of less than 12 hours. The intermediate-acting benzodiazepines have half-lives of 12 to 24 hours. While the longest lasting benzodiazepines have half lives over 24 hours. See the individual sections on the specific benzodiazepines for more information. Due the the extremely long half-lives of some benzodiazepines (from several days to over a week), drug interactions must be more carefully considered. Therefore, the long-acting benzodiazepines have a greater associated risk. Taking flurazepam for instance and then drinking heavily even a couple of days later could cause potentially fatal interactions.

Common Brands

• Alprazolam (Xanax)
• Diazepam (Valium)
• Clonazepam (Klonopin)
• Flunitrazepam (Rohypnol)
• Lorazepam (Ativan)
• Nimetazepam (Erimin)
• Temazepam (Restoril)
• Triazolam (Halcion)