Hypotensive and bradycardic effects of talipexole (B-HT 920) in anaesthetized rabbits are antagonized by metoclopramide but not by yohimbine.
The interactions of talipexole (B-HT 920) and clonidine with selective alpha-adrenoceptor antagonists, yohimbine (alpha 2) and prazosin (alpha 1), as well as with dopamine receptor antagonists, metoclopramide (D2), domperidone (D2) and SCH23,390 (D1) were investigated in anaesthetized rabbits after i.v. administration. Both talipexole (0.03-0.1 mg/kg) and clonidine (0.01-0.03 mg/kg) dose-dependently induced hypotension and bradycardia. Talipexole had a shorter duration of action. The hypotensive effect of the alpha 2-adrenoceptor and D2 agonist talipexole (0.03 mg/kg) was antagonized by pretreatment with metoclopramide (3 mg/kg) or domperidone (0.3-3 mg/kg), but not with yohimbine (3 mg/kg), prazosin (0.1 mg/kg) or SCH23,390 (1 mg/kg). Its bradycardic effect was antagonized only by metoclopramide (3 mg/kg). The hypotensive and bradycardic effects of clonidine (0.03 mg/kg) were most effectively antagonized by yohimbine (0.3-3 mg/kg). These findings indicate that in anaesthetized rabbits after i.v. administration, talipexole may lower blood pressure by peripheral, and heart rate by central, dopamine D2 agonism.
Palluk
R
R
Department of Pharmacology, Boehringer Ingelheim KG, Germany.
Schilling
J C
JC
Stockhaus
K
K
Peil
H
H
D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors*; D000818:Animals; D001381:Azepines / Q000037:antagonists & inhibitors*; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004294:Domperidone / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D011817:Rabbits; D015016:Yohimbine / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D001552:Benzazepines; D015016:Yohimbine; D004294:Domperidone; C024763:talipexole; D008787:Metoclopramide