China Greatvista Chemicals

Nefazodone

Nefazodone hydrochloride is a phenylpiperazine antidepressant with a mechanism of action that is distinct from those of other currently available drugs. It potently and selectively blocks postsynaptic serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptors and moderately inhibits serotonin and noradrenaline (norepinephrine) reuptake. In short term clinical trials of 6 or 8 weeks' duration, nefazodone produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with imipramine, and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline. The optimum therapeutic dosage of nefazodone appears to be between 300 and 600 mg/day. Limited long term data suggest that nefazodone is effective in preventing relapse of depression in patients treated for up to 1 year. Analyses of pooled clinical trial results indicate that nefazodone and imipramine produces similar and significant improvements on anxiety- and agitation-related rating scales compared with placebo in patients with major depression. Short term tolerability data indicate that nefazodone has a lower incidence of adverse anticholinergic, antihistaminergic and adrenergic effects than imipramine.

Compared with SSRIs, nefazodone causes fewer activating symptoms, adverse gastrointestinal effects (nausea, diarrhoea, anorexia) and adverse effects on sexual function, but is associated with more dizziness, dry mouth, constipation, visual disturbances and confusion. Available data also suggest that nefazodone is not associated with abnormal weight gain, seizures, priapism or significant sleep disruption, and appears to be relatively safe in overdosage. Nefazodone inhibits the cytochrome P450 3A4 isoenzyme and thus has the potential to interact with a number of drugs. Further long term and comparative studies will provide a more accurate assessment of the relative place of nefazodone in the management of major depression. Nonetheless, available data suggest that nefazodone is a worthwhile treatment alternative to tricyclic antidepressants and SSRIs in patients with major depression.

Nefazodone is an antidepressant for oral administration with a chemical structure unrelated to selective serotonin reuptake inhibitors, tricyclics, tetracyclics, or monoamine oxidase inhibitors (MAOI). Nefazodone hydrochloride is a synthetically derived phenylpiperazine antidepressant. The chemical name for nefazodone hydrochloride is 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ether-2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one monohydrochloride. The molecular formula is C25H32ClN5O2•HCl, which corresponds to a molecular weight of 506.5. Nefazodone is a nonhygroscopic, white crystalline solid. It is freely soluble in chloroform, soluble in propylene glycol, and slightly soluble in polyethylene glycol and water.

Nefazodone is a relatively new antidepressant with a chemical structure that is somewhat similar to that of the phenylpiperazine antidepressant, trazodone. The antidepressant action of nefazodone is thought to be dependent on its ability to block postsynaptic serotonin type-2 receptors and inhibit presynaptic serotonin reuptake. Nefazodone also blocks norepinephrine reuptake. Nefazodone does not have a chemical structure similar to the SSRIs, tricyclic anti- depressants, monoamine oxidase inhibitors, bupropion, or venlafaxine. .

Mechanism of Action: The pharmacologic actions of nefazodone involve both the serotonergic and, to a lesser extent, the noradrenergic systems. Within the serotonergic system, nefazodone is a potent antagonist at type 2 serotonin (5-HTÁ) post-synaptic receptors. Nefazodone also inhibits pre-synaptic serotonin (5-HT) reuptake (similar to fluoxetine-type antidepressants) but this mechansim is secondary in importance. Both mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally and this effect is lost with chronic dosing. In addition, nefazodone has been shown to antagonize ¢À-adrenergic receptors. Blockade of beta-adrenergic receptors produces sedation, muscle relaxation, and cardiovascular effects such as hypotension, reflex tachycardia, and minor changes in ECG patterns. Nefazodone has no significant affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, or £ or ¢Á-adrenergic receptors. As with other antidepressants, nefazodone's antidepressant effects may not be noticeable for several weeks. Nefazodone does not inhibit REM sleep.