Nefazodone: A Review of Its Neurochemical Mechanisms, Pharmacokinetics, and Therapeutic Use in Major Depressive Disorder

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He H, Richardson S

Nefazodone: A Review of Its Neurochemical Mechanisms, Pharmacokinetics, and Therapeutic Use in Major Depressive Disorder

CNS Drug Review. 2006 Sept 19;3(1):34-48.

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Abstract

Nefazodone, an antidepressant agent with a phenylpiperazine structure, has a pharmacological profile that is distinct from other antidepressant drugs. Like many other antidepressants, nefazodone inhibits the reuptake of norepinephrine and serotonin from the synaptic cleft. Unlike other antidepressants, nefazodone is also a potent antagonist of 5-HT2 serotonergic receptors. In addition, nefazodone is a weak antagonist of α1-adrenergic receptors, but has little or no affinity for cholinergic, histaminergic, or dopaminergic receptors. In placebo-controlled clinical trials, nefazodone has been found to be an effective antidepressant drug with minimal cardiovascular action and significantly fewer side effects than imipramine. Since nefazodone is an effective antidepressant with a low incidence of serious adverse effects, it may be particularly useful in major depressive disorder patients who are intolerant of the anticholinergic or serotonergic side effects of other antidepressants, or who do not respond to treatment with other antidepressant agents. In this paper, we review the mechanisms of action, the pharmacokinetics, and the antidepressant efficacy of nefazodone.

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