The action of diazepam is due to what is known as allosteric modulation of the GABA-A receptor in the neurons of the brain and spinal cord. This means that diazepam does not bind directly to the binding site of GABA, but to a separate site on the receptor. This increases the affinity of GABA (gammaaminobutyric acid, an important inhibitory neurotransmitter) for the receptor, making it more likely to open. This results in the depressant effect of diazepam.
Diazepam is absorbed in the gastrointestinal tract and reaches maximum plasma concentration after approximately 1-1.5 hours. Plasma protein binding is 98-99%. Diazepam is degraded in the liver by the enzymes of the CYP450 system. The two enzymes CYP3A4 and CYP2C19 are mainly involved. The resulting metabolites are glucuronidated and almost entirely excreted in the urine. The elimination half-life is 1-2 days.
Concomitant use with drugs that are also cleared by the CYP3A4 or CYP2C19 enzymes may result in increased levels of diazepam. These include: Cimetidine, omeprazole, disulfiram, ketoconazole, fluvoxamine and fluoextine. Combination with drugs that have the same or similar effect on the CNS (antidepressants, sedatives, neuroleptics, antiepileptics, anxiolytics, HIV protease inhibitors) should also be avoided at all costs. Furthermore, diazepam must not be combined with levodopa, theophylline, phenytoin, phenobarbital and muscle relaxants.