Evidence that SK & F 104078 does not differentiate between pre- and postjunctional alpha 2-adrenoceptors.

We have investigated the proposed postjunctional selectivity of the alpha 2-adrenoceptor antagonist SK & F 104078 employing the pithed rat, rat isolated atrium and human saphenous vein preparations. In the pithed rat, SK & F 104078 (5 mg kg-1) produced a 20-fold shift in the prejunctional ID50 (concentration of agonist producing 50% inhibition of the cardioacceleration to a single stimulus) and a 3-fold shift in the postjunctional ED50 (concentration producing 50% of maximum rise in diastolic blood pressure) of the alpha 2-adrenoceptor agonist xylazine. However, the alpha 2-adrenoceptor antagonist yohimbine also showed apparent selectivity for prejunctional receptors in the pitched rat. In the rat isolated atrium, yohimbine was approximately 10 times more potent than SK & F 104078 at enhancing the stimulation-evoked release of tritium in tissues preincubated with (3H)-noradrenaline. In the human saphenous vein, yohimbine and SK & F 104078 had pA2 values of 7.40 and 6.33, respectively, against contractions to noradrenaline, so that yohimbine was again approximately ten times more potent than SK & F 104078. In conclusion, SK & F 104078 behaved like yohimbine in its relative potencies at pre- and postjunctional alpha 2-adrenoceptors both in vivo and in vitro, so that we fail to find any selectivity of SK & F 104078 for postjunctional alpha 2-adrenoceptors.