Methylphenidate-like effects of the new antidepressant drug nomifensine (HOE 984)

Nomifensine (HOE 984) belongs to a chemically new class of drugs with reported antidepressant properties. Nomifensine, like methylphemidate, d-amphetamine and apomorphine, induces strong, intense stereotypes behaviour in the rat. The nomifensine-induced stereotyped behaviour was completely antagonized by pretreatment with reserpine (7.5 mg/kg, 18 h) but not by short-time pretreatment with alpha-methyltyrosine (250 mg/kg, 2 h.) Nomifensine thus differs from d-amphetamine and apomorphine but resembles methylphenidate on stereotyped behaviour. Nominfensine, M1 (8-amino-2-methyl-4-(4-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline fumarate) (Hoechst), methylphenidate and d-amphetamine induced a strong increase in the brain level of homovanillec acid (HVA), whereas the dopamine uptake inhibitor benztropine induced no changes in HVA and cocaine induced only a small increase. Nomifensine and the M1 metabolite, like methylphenidate, also increased 3,4-dihydroxyphenylacetic acid (DOPAC) whereas amphetamine, apomorphine, benztropine and cocaine decreased this dopamine metabolite. This suggests that the stereotyped licking and/or biting activities in the rat are related to dopamine releasing properties of nomifensine, methylphenidate and amphetamine. This is further supported by an inverse relationship between the in vitro dopamine uptake inhibitory concentrations and the sterotypy-inducing dose levels of nomifensine and d-amphetamine. Amphetamine caused a strong, and nomifensine and apormorphine a week increase in brain 3-methoxy-4-hydroxyphenylglycol (MOPEG).