Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat

The antidepressant minaprine (3-(2-morpholino-ethylamino) 4-methyl 6-phenyl pyridazine, dihydrochloride) and its main metabolites were examined for their monoamine oxidase (MAO) inhibitory effects in the rat. In our experimental conditions, minaprine displayed in vitro a very weak affinity for brain MAO A and B with IC50S close to 1 mM. However, ex vivo, after intraperitoneal administration, this drug behaved as a specific and short-acting type A MAO inhibitor (MAOI) of mild potency (ED50 = 12.8 mg/kg). In comparison, the reversible type A MAOIs, moclobemide and cimoxatone, were respectively 14 and 15 times more potent. When administered orally, minaprine proved to be considerably less active. The results presented in this study suggest that minaprine inhibits MAO A mainly after being converted into active metabolites. However, the chloroform extractable metabolites were found inactive in vitro towards this enzyme, suggesting that MAO inhibitory activity is mediated by one or more other non-identified metabolites.