Other minor active metabolites include oxazepam and temazepam. DiazepamВ is mostly brokenВ down by the microsomal enzymes CYP2C19 and CYP3A4 enzymes to several active metabolites, mainlyВ desmethyldiazepam. While there is a moderately quick onset of action, the drug quickly redistributes. Mediation of the sedative, amnestic, and anticonvulsant effects of diazepam is through receptor binding within the cortex, thalamus, and cerebellum. Allosteric binding within the spinal cord and motor neurons is the primary mediator of the myorelaxant effects seen with diazepam. Specifically, the allosteric binding within the limbic system leads to the anxiolytic effects seen with diazepam. ThisВ shift in charge leads to aВ hyperpolarization of the neuronal membrane and reduced excitability of theВ neuron. The allosteric binding of diazepam at theВ GABA-AВ receptor leads to an increase in the frequency at which the chloride channel opens, leading to an increased conductance of chloride ions. Д«enzodiazepines exert their effects by facilitating the activity of gamma-aminobutyric acid(GABA) at various sites.В Specifically, benzodiazepines bind at an allosteric site at the interface between the alpha and gamma subunits onВ GABA-AВ receptor chloride ion channels. Off-label (non-FDA approved) use for diazepam includes sedation in the ICU and short-term treatment of spasticity in children with cerebral palsy. Дiazepam is FDA approved for the management of anxiety disorders, short-term relief of anxiety symptoms, spasticity associated with upper motor neuron disorders, adjunct therapy for muscle spasms, preoperative anxiety relief, management of certain refractory epilepsy patients and adjunct in severe recurrent convulsive seizures, and an adjunct in status epilepticus. Benzodiazepines have largely replaced barbiturates in treating anxiety and sleep disorders because of their improved safety profile, fewer side effects, and flumazenil(antagonist)В availability that can reverse oversedationВ in cases of benzodiazepine intoxication.

In the setting of acute alcohol withdrawal, diazepam is useful for symptomatic relief of agitation, tremor, alcoholic hallucinosis, and acute delirium tremens. It is a fast-acting, long-lasting benzodiazepine commonly used to treat anxiety disorders and alcohol detoxification, acute recurrent seizures, severe muscle spasms, and spasticity associated with neurologic disorders. At present the most common combination of antidotes against soman, consisting of obidoxime and atropine, as well as a prospective combination containing oxime HI-6 and atropine should be supplemented with diazepam not only to prevent centrally induced seizures and tonic-clonic convulsions but also to increase the ability of such antidotal therapy to eliminate acute lethal toxicity of soman.Diazepam is an anxiolytic benzodiazepine, first patented and marketed in the United States in 1963. At the same time, the addition of diazepam to the antidotal therapy does not change the difference in the efficacy of the antidotal therapy in dependence on the selected anticholinergic agent or acetylcholinesterase reactivator. In the case of employment of anticholinergic agents with prevailing central effects, such as benactyzine, biperiden, or scopolamine, the addition of diazepam will not significantly influence the therapeutic efficacy of the antidotal therapy regardless of the selected aetylcholinesterase reactivator. The obtained results show that addition of diazepam to the basic antidotal therapy increases the ability of the antidotal therapy to eliminate acute lethal effects of soman if it includes atropine as an anticholinergic agent regardless of the employed type of acetylcholinesterase reactivator. The efficacy of the basic antidotal therapy of acute intoxications by soman evaluated in this way was compared with the effect of an antidotal therapy enriched with diazepam, a drug with anticonvulsive action. Experiments on male rats examined the effect of a basic antidotal therapy consisting of various types of anticholinergic substances and reactivators of acetylcholinesterase on the lethal effects of the highly toxic organophosphorous compound soman by means of determination of the medium lethal dose of soman in 24-hour survival of experimental animals.

Diazepam antidote dose