Effects of PN 200-110, a new calcium antagonist, on alpha 1- and alpha 2-adrenoceptor mediated vasoconstriction elicited by selective alpha-adrenoceptor agonists and catecholamines in the pithed rat.

The inhibitory action of PN 200-110, a novel calcium antagonist, on alpha 1- and alpha 2-adrenoceptor mediated pressor effects elicited by selective alpha-adrenoceptor agonists and catecholamines was studied in pithed rats. The pressor effects of the selective alpha 1-adrenoceptor agonist cirazoline were only slightly influenced by PN 200-110 (0.1 mg/kg). On the other hand, PN 200-110 efficiently inhibited the hypertensive effects of the selective alpha 2-adrenoceptor agonist B-HT 920 in a dose-dependent way, thereby reducing the maximal response considerably (pD2' = 7.30). The alpha 1-adrenoceptor mediated pressor responses of adrenaline and noradrenaline, obtained after pretreatment with propranolol and the selective alpha 2-adrenoceptor antagonist yohimbine, were slightly inhibited by PN 200-110, without influencing maximal responses. PN 200-110 inhibited the alpha 1-adrenergic pressor effects of noradrenaline better than those of adrenaline. The alpha 2-adrenoceptor mediated pressor effects of the cathecholamines obtained after pretreatment with propranolol and the selective alpha 1-adrenoceptor antagonist prazosin, were highly susceptible to blockade by PN 200-110 except for the high doses (300 micrograms/kg) of adrenaline. The present study establishes the pronounced calcium entry inhibitory potency of PN 200-110 and confirms and extends previous observations that blockade of calcium entry preferably impairs alpha 2-adrenoceptor mediated vasoconstriction in vivo, when compared to that elicited by alpha 1-adrenoceptor stimulation.