VASCULAR AND CARDIAC EFFECTS OF ALPHA-METHYL-5-HT AND DOI ARE MEDIATED BY DIFFERENT 5-HT RECEPTORS IN THE PITHED RAT

In pithed rats, alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) increased blood pressure and heart rate, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) almost exclusively increased blood pressure and 1-(3-chlorophenyl)piperazine (mCPP), heart rate. The maximal responses relative to 5-HT indicate that alpha-methyl-5-HT may be a full agonist at vascular and cardiac 5-HT receptors, DOI a partial agonist at both receptors and mCPP a full agonist at cardiac 5-HT receptors but a partial agonist at vascular 5-HT receptors. The alpha1-adrenoceptor antagonist, 2-[2-[4(o-methoxyphenyl)-piperazine-1-yl]-ethyl]4,4-dimethyl -1,3(2H-4H) isoquinolinedione (AR-C 239), did not change the pressor and tachycardiac effects of alpha-methyl-5-HT and DOI, excluding the participation of alpha1-adrenoceptors. 4-Isopropyl-7-methyl-9-(2-hydroxy-1-methylpropoxycarbonyl) 4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline (LY 53857), spiperone and ketanserin but not propranolol antagonised the pressor effect of alpha-methyl-5-HT, indicating a preferential participation of 5-HT2 receptors although an implication of 5-HT1C receptors could not be ruled out. Spiperone, spiperone plus propranolol, LY 53857, ketanserin and propranolol antagonised the pressor effects of DOI suggesting the stimulation of both 5-HT2 and 5-HT1C receptors. Propranolol and spiperone plus propranolol suppressed the weak increase in heart rate induced by DOI, indicating the stimulation of 5-HT1C receptors. However, propranolol and LY 53857 only antagonised the tachycardiac effects of a high dose of alpha-methyl-5-HT. We hypothesised that the pressor and tachycardiac effects of these agonists may be mediated by 5-HT2 and 5-HT1c receptors, respectively. However, the availability of specific 5-HT1C and/or 5-HT2 receptor antagonists is necessary to verify our hypothesis and before a clear-cut conclusion can be drawn.