Biochemical effects of minaprine on striatal dopaminergic neurons in rats

Author:

Ferretti P1,Algeri S1,Benfenati F1,Cimino M1,Ferretti C1,Garattini S1,Lipartiti M1

Affiliation:

1. Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via Eritrea, 62, 20157-Milan, Italy

Abstract

Abstract The biochemical effects of minaprine, a new psychotropic drug, were investigated on striatal dopaminergic neurons in the rat. Minaprine did not displace [3H]spiperone in-vitro binding from striatal membranes but had clear effects on dopamine (DA) metabolites. Homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were significantly decreased in a dose-dependent manner after intraperitoneal administration of minaprine 30 min before killing. In rats injected with minaprine 15 mg kg−1 i.p. at different intervals, the decrease in striatal HVA and DOPAC was time-dependent and a concomitant rise in 3-methoxytryramine (3-MT) concentrations was observed. The maximum of these effects was reached 30 min after minaprine. When administered 5 min after a monoamineoxidase (MAO) inhibitor (pargyline, 100 mg kg−1 i.p.) and 30 min before killing, minaprine did not affect pargyline-induced changes in HVA, DOPAC and 3-MT levels. This together with other data suggests that minaprine affects DA metabolism by acting, at least partially, at presynaptic level through in-vivo inhibition of MAO activity.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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