title: The effect of urapidil on cardiac alpha- and beta-adrenoceptors.
abstract: In the present study the effects of the antihypertensive drug urapidil on cardiac adrenoceptors in various regions of the heart were analyzed. On the isolated rabbit papillary muscle urapidil was found to produce a competitive antagonism against the alpha 1-agonist phenylephrine with a pA2-value of 6.4 in the presence of the beta-antagonist sotalol (5 X 10(-5) mol/l). In the same preparation urapidil also antagonized the positive inotropic effects evoked by the beta-adrenoceptor agonist isoprenaline yielding a pA2-value of 5.9. An antagonism against the positive inotropic effect of isoprenaline with the same pA2-value could also be demonstrated in guinea pig left atria. For further characterization of urapidil its effect against the beta 2-adrenoceptor agonist fenoterol on the carbachol contracted tracheal chain of the guinea pig was investigated. A weak antagonism with a pA2-value of 4.9 was observed. Thus the beta 1-adrenolytic potency of urapidil was found to be about 10 times higher than the beta 2-adrenolytic one. On the isolated perfused rabbit heart urapidil inhibited the electrically evoked increase in heart rate by 27 and 63% in a concentration of 10(-6) and 10(-5) mol/l, respectively, whereas the stimulation induced noradrenaline release was increased by 25 and 51%. This rise in noradrenaline release by urapidil was antagonized by clonidine 10(-7) and 10(-6) mol/l. From these results it can be concluded that urapidil acts not only as an antagonist at cardiac alpha 1- and beta-adrenoceptors, but also on alpha 2-adrenoceptors located presynaptically. The antagonism at these receptors against endogenous noradrenaline leads to an enhanced transmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005280:Fenoterol / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000648:ultrastructure; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
chemical_list: D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D005280:Fenoterol; C015568:urapidil; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine