On the mode of action of heptaminol
Grobecker, H.; Grobecker, H.
Arzneimittel-Forschung 26(12): 2167-2171
1976
ISSN/ISBN: 0004-4172 PMID: 1037266 Document Number: 97914
The effect of heptaminol, an aliphatic amine with an alcoholic group on carbon 2, on sympathetic nerves and on isolated chromaffine granules was infestigated. In cats, heptaminol caused long-lasting, dose-dependent pressor effects accompanied by tachycardia and contractions of the nictitating membrane. In comparison with tyramine, heptaminol was 100 times less potent in increasing blood pressure and 10 times less effective in inducing contractions of the nictitating membrane. The rise in blood pressure as well as tachycardia and contraction of the nictitating membrane were diminished by cocaine. After pretreatment with cocaine, heptaminol in high doses caused short-lasting depressor effects. Also in rats the pressor effect of heptaminol was weaker but of longer duration than that of tyramine. The dose-response curve was depressed by pretreatment with reserpine. The tachycardia induced by heptaminol was markedly diminished after pretreatment with reserpine. After repeated injections heptaminol reduced the norepinephrine content of the rat heart by 20-40%, Tyramine and hexylamine were more effective than heptaminol in depleting the norepinephrine stores of the heart (50-60%). In fluorescence microscopic investigations on sympathetic nerves (rat iris) depleted of norepinephrine by reserpine, the uptake of alpha-methylnorepinephrine could be inhibited or prevented by heptaminol. The spontaneous release of catecholamines from isolated bovine chromaffine granules was enhanced (+30%) by heptaminol or methamphetamine in high concentrations. In lower concentrations, however, both drugs reduced the uptake of 14C-epinephrine in isolated medullary granules by 20-40%. In addition a non-specific papaverine-like spasmolytic effect of heptaminol could be demonstrated. The results suggest that heptaminol exerts its pharmacological action by interfering with release and uptake of norepinephrine.