The canine external carotid vasoconstrictor 5-HT1 receptor: blockade by 5-HT1B (SB224289), but not by 5-HT1D (BRL15572) receptor antagonists

In vagosympathectomised dogs pre-treated intravenously (i.v.) with mesulerg ine (300 mu g/kg), I-min intracarotid (i.c.) infusions of 5-hydroxytryptami ne (5-HT; 0.3-30 mu g/min) and sumatriptan (1-30 mu g/min) dose-dependently decreased external carotid blood flow, without affecting mean blood pressu re or heart rate. Treatment with the selective 5-HT1B receptor antagonist S B224289 (2,3,6,7-tetrahydro-1'-methyl-5-[2'-methyl-4'(5-methyl-1,2,4-oxadia zol-3-yl) biphenyl-4-carbonyl]furo[2,3f]indole-3-spiro-4'-piperidine hydroc hloride; 30-300 mu g/kg, i.v.) produced a potent, specific and dose-depende nt blockade of this response, whereas the selective 5-HT1D receptor antagon ist BRL15572(1-(3-chlorophenyl)-4-[3,3-diphenyl(2-(S, R) hydroxypropanyl)pi perazine]hydrochloride 30-300 mu g/kg, i.v.) was ineffective. It is conclud ed that mainly 5-HT1B, but not 5-HT1D receptors mediate the canine external carotid vasoconstriction by 5-HT and sumatriptan. (C) 1998 Elsevier Scienc e B.V. All rights reserved.