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Pharmacological analysis of the cardiac effects of 5‐HT and some 5‐HT receptor agonists in the pithed rat
Author(s) -
Dabiré H.,
ChaoucheTeyara K.,
Cherqui C.,
Fournier B.,
Schmitt H.
Publication year - 1992
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1992.tb00116.x
Subject(s) - ketanserin , endocrinology , medicine , 5 ht receptor , pindolol , chemistry , idazoxan , agonist , pharmacology , receptor , partial agonist , heart rate , serotonin , antagonist , prazosin , blood pressure
Summary— A pharmacological analysis of the effects of 5‐HT on heart rate has been performed in the pithed rat. 5‐HT induced a dose‐dependent increase in heart rate whereas 5‐HT, receptor agonists — 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT), 5‐methoxy‐ N,N ‐dimethyl‐tryptamine (5‐MeODMT), 5‐methoxy 3‐(1,2,3,6‐tetrahydro‐4‐piridinyl) 1H indole (RU 24969) and 1‐(m‐trifluoromethylphenyl)‐piperazine (TFMPP) — failed to increase heart rate. The increase in heart rate induced by the selective 5‐HT 2 receptor agonist 1‐(2,5‐dimethoxy‐4‐iodo‐phenyl)‐2‐aminopropane (DOI) was not significant. The dose‐response curve to 5‐HT for its tachycardic effects was shifted two‐fold to the right by ketanserin and LY 53857 and nine‐fold to the right by methiothepin. The effects of high doses of 5‐HT (higher than 100 μg/kg iv) were antagonized by methiothepin, (‐)propranolol, 2‐{2‐[4(O‐methoxyphenyl)‐piperazine‐1‐yl]‐ethyl}4,4‐dimethyl‐1,3 (2H‐4H) isoquinoline‐dione (AR‐C 239) and by pretreatment with reserpine. The 5‐HT 1 receptor antagonists, pindolol and spiroxatrine, the 5‐HT 3 receptor antagonist MDL 72222 and the α 2 ‐adrenoceptor blocking agent idazoxan failed to antagonize the tachycardia induced by 5‐HT. It is concluded that in the pithed rat, the tachycardia induced by 5‐HT remained unexplained (implication of 5‐HT 2 receptors probably different from the classical vascular 5‐HT 2 receptor, or implication of 5‐HT 1C receptors?). Moreover, at high doses (higher than 100 μ/kg iv), 5‐HT may increase heart rate by releasing catecholamines.