Investigations on the mechanism of positive inotropic action of (+) -tranylcypromine in isolated guinea-pig atria
Dénes, B.; Greeff, K.
Arzneimittel-Forschung 34(3): 266-270
1984
ISSN/ISBN: 0004-4172 PMID: 6539606 Document Number: 231431
Investigations on the mechanism of the positive inotropic action of (+)-tranylcypromine (TCP) on left, electrically stimulated, isolated guinea-pig atria led to the following results: In contrast to (-)-TCP, the positive inotropic action of (+)-TCP on the guinea-pig atria is not abolished, but only weakened by pretreating animals with reserpine. The positive inotropic effect of indirectly acting sympathomimetics, such as tyramine or methamphetamine, on isolated atria of reserpine pretreated guinea pigs recovers within 15-30 min of incubation with (+)-TCP. The same applies to other inhibitors of MAO-A, such as clorgiline and pargyline as well as selegiline (deprenyl) in higher concentrations. Inhibitors of norepinephrine (noradrenaline) synthesis as alpha-methyl-p-tyrosine and FLA-63 (bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)-disulphide] prevent the positive inotropic action of (+)-TCP on atrial preparations of reserpine pretreated guinea pigs, and abolish the (+)-TCP induced restitution of the effects of tyramine and methamphetamine. A destruction of adrenergic nerves using 6-hydroxydopamine also prevents the positive inotropic action of (+)-TCP. These results suggest that (+)-TCP increases the net neuronal synthesis of catecholamines.