TYRAMINE ANTAGONISTIC PROPERTIES OF AGN 1135, AN IRREVERSIBLE INHIBITOR OF MONOAMINE OXIDASE TYPE B

Abstract

1 The effects of the irreversible monoamine oxidase (MAO) inhibitors, AGN 1133, AGN 1135 and (−)-deprenyl, on tyramine and noradrenaline responses and uptake of [³H]-metaraminol were investigated in the isolated vas deferens of the rat. Uptake of [³H]-metaraminol and [³H]-octopamine was compared in mouse vas deferens. The modification of tyramine and noradrenaline-induced pressor responses by AGN 1133 and AGN 1135 was examined in anaesthetized rats and cats. 2 AGN 1133 (7.5 × 10⁻⁶m) greatly potentiated responses to tyramine in the rat isolated vas deferens. Both AGN 1135 and (−)-deprenyl inhibited tyramine responses selectively at concentrations above 10⁻³m (which caused almost complete inhibition of MAO types A and B) but tyramine responses were potentiated on washing out the inhibitors. 3 AGN 1135 (10⁻⁴m) and (−)-deprenyl (10⁻⁵m) inhibited [⁻³H]-metaraminol uptake by about20% in rat and mouse vas deferens; neither inhibitor affected [⁻³H]-octopamine uptake in mouse vas deferens. Desmethylimipramine (10⁻⁶m) inhibited amine uptake by more than 70%. 4 AGN 1133 (1.5 mg/kg) potentiated pressor responses to tyramine in rats and cats whereas AGN 1135 (1.5 mg/kg) did not. 5 AGN 1135 possesses tyramine antagonistic activity which is qualitatively similar to that of (−)-deprenyl but which cannot satisfactorily be explained by inhibition of neuronal or granular amine uptake.