Cardiovascular properties of a 5-HT1-like receptor agonist, 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) in normotensive anaesthetized rats.
Intravenous administration of the putative 5-HT1-like receptor agonist RU 24969 (10-1000 micrograms/kg) in anaesthetized rats induced a decrease in heart rate and blood pressure. The bradycardia was reduced, but not suppressed, by tertatolol, bilateral vagotomy or the combination of both treatments. The alpha 1-adrenoceptor blocking agent, AR-C 239, decreased the bradycardia induced by high doses of RU 24969. After treatment with hexamethonium, RU 24969 induced an increase in arterial blood pressure. The hypotensive response induced by RU 24969 was not altered by atropine. The hypotensive and bradycardic effects of RU 24969 were antagonized by methysergide (5-HT1-like receptor antagonist) and in part by spiroxatrine (5-HT1A receptor antagonist). Ketanserin (5-HT2 receptor antagonist) potentiated the effects of low doses of RU 24969. The cardiovascular effects of RU 24969 were antagonized neither by MDL 72222 nor by ICS 205-930 (5-HT3 receptor antagonists). The present results suggest that the cardiovascular effects of RU 24969 seem to be due to the stimulation of 5-HT1-like receptors. The participation of both 5-HT1A and 5-HT1B receptors subtypes has been considered. The results suggest a centrally-mediated inhibition of sympathetic tone and increase in vagal tone in the cardiovascular effects of RU 24969.
Cherqui
C
C
INSERM U 228, Faculté de Médecine Broussais Hôtel-Dieu, Paris, France.
Dabire
H
H
Fournier
B
B
Schmitt
H
H
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006633:Histamine Antagonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011970:Receptors, Histamine H2 / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D006633:Histamine Antagonists; D007211:Indoles; D011970:Receptors, Histamine H2; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole