The alpha 2-adrenoceptor selectivities and haemodynamic effects of WY26392 and yohimbine in the anaesthetised dog.
The selectivities of WY26392 and yohimbine for prejunctional alpha 2-adrenoceptors have been evaluated in the anaesthetised dog. Clonidine inhibited the tachycardia evoked by cardiac sympathetic nerve stimulation, WY26392 and yohimbine reversed this effect by 50% at doses of 3.3-12 and 7.5-69.5 micrograms/kg respectively, depending upon the frequency of nerve stimulation. The alpha 1-adrenoceptor agonist phenylephrine evoked a pressor response which was reduced by 50% following approximately 1.0 mg/kg of either antagonists. Due to its greater potency at alpha 2-adrenoceptors, WY26392 consistently exhibited a greater selectivity than yohimbine for this receptor. The haemodynamic evaluation of WY26392 and yohimbine revealed that low doses of these compounds (0.03-0.1 mg/kg i.v.) increased systolic blood pressure, heart rate and dp/dtmax. WY26392 evoked a small rise in diastolic blood pressure over this dose range. These increases may be due to an increase in sympathetic nerve activity resulting from alpha 2-adrenoceptor blockade. Higher doses of these compounds reduced these cardiovascular parameters, possibly as a result of alpha 1-adrenoceptor blockade.
Paciorek
P M
PM
Shepperson
N B
NB
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D011807:Quinolizines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; C038537:Wy 26392