Some pharmacological properties of Wy 27127 a more selective alpha 2:alpha 1-adrenoceptor antagonist than idazoxan in vitro.
Wy 27127 and idazoxan were approximately equipotent as antagonists at alpha 2-adrenoceptors as estimated by their ability to block clonidine-induced inhibition of electrically-evoked contractions of the rat isolated vas deferens. Idazoxan was seven times as potent as Wy 27127, as an antagonist at alpha 1-adrenoceptors as indicated by blockade of methoxamine-induced contractions of the rat isolated anococcygeus muscle. Thus, the alpha 2:alpha 1 selectivity ratio, as calculated from these tests was 407 for Wy 27127 and 76 for idazoxan. Wy 27127 and idazoxan were equipotent in enhancing stimulation-evoked overflow of tritium from rabbit isolated pulmonary arteries preloaded with [3H]-noradrenaline as expected for alpha 2-adrenoceptor antagonists. At higher concentrations both compounds reduced the stimulation-evoked contraction of the pulmonary artery but idazoxan was 15 times as potent as Wy 27127 in this respect. Neither compound had marked antagonist actions at 5-hydroxytryptamine (D), muscarinic, presynaptic dopamine or histamine (H1) receptors or at beta 1-adrenoceptors. Thus, idazoxan and Wy 27127 were equipotent alpha 2-adrenoceptor antagonists in vitro, however, the alpha 2:alpha 1 selectivity of Wy 27127 was considerably greater than that of idazoxan by virtue of weaker alpha 1-adrenoceptor antagonism.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004558:Electric Stimulation; D006633:Histamine Antagonists / Q000494:pharmacology; D019329:Idazoxan; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D006633:Histamine Antagonists; D011807:Quinolizines; D011954:Receptors, Dopamine; C051828:Wy 27127; D019329:Idazoxan