Niaprazine, a selective brain catecholamine depletor.

Niaprazine (30–240 mg/kg i.p.) lowered rat brain levels of noradrenaline and dopamine, but did not alter levels of 5-hydroxytryptamine. The maximum depletion (65–70%) was observed 30 min after an injection of 120 mg/kg (i.p.) niaprazine, and total depletion could not be achieved by increasing the dose further. The reduction in levels of catecholamines was short-lasting, and was accompanied by an increase in brain levels of the metabolites DOPAC and MOPEG-SO₄. In contrast to niaprazine, tetrabenazine (20 mg/kg i.p.) lowered the brain levels of 5-hydroxytryptamine as well as the catechol-amines, and increased brain levels of their metabolites, 5-HIAA, DOPAC and MOPEG-SO₄. Reduced brain concentrations of catecholamines were observed 24 hr after an injection of reserpine (1 mg/kg i.p.). Pretreatment with tetrabenazine (20 mg/kg i.p.) prevented the reserpine-induced depletion of brain catecholamines, whereas pretreatment with niaprazine (60 or 180 mg/kg i.p.) did not alter the reserpine-induced depletion. The results indicate that niaprazine depletes brain catecholamines, but differs in its profile of action from reserpine and tetrabenazine.