Potentiating actions of tranylcypromine and moclobemide on the sympathomimetic activity of dopamine.
Ex vivo investigations were carried out to study the potentiating actions of the MAOIs moclobemide and tranylcypromine on peripheral alpha- and beta-adrenergic effects of dopamine. Isolated rat vas deferens and atria were used. Preliminary experiments showed that both moclobemide and tranylcypromine did not affect the response to noradrenaline, while they enhanced the response to tyramine. By comparison of the responses to dopamine in control and reserpinized rats, it was shown that dopamine acts in a direct and indirect manner on both the tissues tested. Two concentrations (20, 40 mg/kg, i.p.) of moclobemide were tested and administered at different time periods (2, 5 or 24 h) before the animals were sacrificed. Two concentrations (2, 20 mg/kg, i.p.) of tranylcypromine were tested at different intervals of time (2, 24 h). The results obtained pointed out that: (1) Moclobemide 20 mg/kg potentiated the alpha-adrenergic response to dopamine only 2 h after administration while 40 mg/kg exerted a potentiation which was evident not only 2 but also 5 h after administration. Both doses were ineffective 24 h after administration. (2) Moclobemide 20 and 40 mg/kg potentiated the beta-adrenergic response to dopamine. The effect was present 2 and 5 h after administration but it was absent 24 h after. (3) Tranylcypromine 20 mg/kg potentiated the alpha-adrenergic response to dopamine: this effect was present after 2 h from pretreatment and was still evident after 24 h. The lower concentration of tranylcypromine (2 mg/kg) enhanced the response to dopamine only after 24 h from pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Grana
E
E
Institute of Pharmacology, Faculty of Pharmacy, University of Pavia, Italy.
Barbieri
A
A
Zonta
F
F
Lucchelli
A
A
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation; D008297:Male; D020912:Moclobemide; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014191:Tranylcypromine / Q000008:administration & dosage / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation
D001549:Benzamides; D014191:Tranylcypromine; D020912:Moclobemide; D004298:Dopamine; D009638:Norepinephrine