化合物信息

Drug Groups

illicit; approved

Description

A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity. It is used in the treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant, and in the management of alcohol withdrawal syndrome. (From Martindale, The Extra Pharmacopoeia, 30th ed, p589)

Indication

Used in the treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant, and in the management of alcohol withdrawal syndrome.

Pharmacology

Diazepam, a benzodiazepine, generates the same active metabolite as chlordiazepoxide and clorazepate. In animals, diazepam appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. Diazepam, unlike chlorpromazine and reserpine, has no demonstrable peripheral autonomic blocking action, nor does it produce extrapyramidal side effects; however, animals treated with diazepam do have a transient ataxia at higher doses. Diazepam was found to have transient cardiovascular depressor effects in dogs. Long-term experiments in rats revealed no disturbances of endocrine function. Injections into animals have produced localized irritation of tissue surrounding injection sites and some thickening of veins after intravenous use.

Toxicity

Symptoms of overdose include somnolence, confusion, coma, and diminished reflexes. Respiration, pulse and blood pressure should be monitored.

Affected Organisms

Biotransformation

Hepatic via the Cytochrome P450 enzyme system. The main active metabolite is desmethyldiazepam, in addition to minor active metabolites including temazepam and oxazepam.

Absorption

Essentially complete, with a bioavailability of 93%.

Half Life

Biphasic 1-2 days and 2-5 days, active metabolites with long half lives.

Protein Binding

98.5%

Elimination

Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates.

Distribution

* 0.8 to 1.0 L/kg [young healthy males]

Clearance

* 20-30 mL/min

References

External Links