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Review
. 2014 Apr 16;5(4):253-60.
doi: 10.1021/cn5000056. Epub 2014 Feb 27.

Classics in chemical neuroscience: diazepam (valium)

Nicholas E Calcaterra  1 , James C Barrow
Affiliations
Review

Classics in chemical neuroscience: diazepam (valium)

Nicholas E Calcaterra et al. ACS Chem Neurosci. .

Abstract

Diazepam (Valium) is among the most successful drugs from the onset of the psychopharmacological revolution that began during the 1950s. Efficacious in treating a wide-spectrum of CNS disorders, including anxiety and epilepsy, it set the standard for pharmacotherapy in terms of potency, onset of action, and safety. In this Review, the legacy of diazepam to chemical neuroscience will be considered along with its synthesis, pharmacology, drug metabolism, adverse events and dependence, clinical use, and regulatory issues.

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Figures

Figure 1
Figure 1
First marketed benzodiazepines and the classical sedative hypnotics.
Scheme 1
Scheme 1. Several Routes to Diazepam Disclosed by Sternbach and Colleagues at Roche
Scheme 2
Scheme 2. Metabolic Fate of Diazepam through the Principally Acting CYP 450 Enzymes, Predominately via Demethylation to 10 Followed by Hydroxylation
Notably, each major metabolite was developed and separately marketed.
Figure 2
Figure 2
Notable diazepam analogues and second generation compounds.
See this image and copyright information in PMC

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