Effect of the optical isomers of YM-12617 on increased intra-urethral pressure induced by phenylephrine in anaesthetized dogs.

1. Effects of the individual optical isomers of YM-12617 (R, S 5-[2-[[2-(o-ethoxyphenoxy)ethyl]-amino]propyl]-2- methoxybenzenesulphonamide HCl, (+/-)-YM), a potent selective alpha 1-adrenoceptor antagonist, on the increase in intraurethral pressure (IUP) and diastolic blood pressure (DBP) induced by phenylephrine were evaluated in pentobarbital-anaesthetized female dogs. 2. Phenylephrine (0.1-30 micrograms kg-1 i.v.), an alpha 1-adrenoceptor agonist, dose-dependently increased IUP and DBP. 3. alpha-adrenoceptor antagonists (i.v.) dose-dependently antagonized the increase in IUP and DBP induced by phenylephrine, with a potency ranking of R(-)-YM greater than (+/-)-YM greater than prazosin greater than phentolamine greater than S(+)-YM greater than yohimbine. 4. These results suggest that the alpha 1-adrenoceptor mediates the increase in IUP as well as DBP in anaesthetized dogs, and that alpha 1-adrenoceptors in the urethra and arteries show a stereochemical preference for R(-)-YM.