Relationship between alpha 2-adrenoceptor occupancy and response for B-HT 933 in canine saphenous vein

The relationship between alpha 2-adrenoceptor occupancy and contractile response for B-HT 933 was investigated in canine saphenous vein. B-HT 933 produced a concentration-dependent, alpha 2-adrenoceptor mediated contractile response in canine saphenous vein with an ED50 of 0.65 microM. The dissociation constant (KA) of B-HT 933 was calculated to be 5 microM. The relationship between alpha 2-adrenoceptor occupancy and contractile response for B-HT 933 in canine saphenous vein was hyperbolic, typical of full agonists or agonists with high intrinsic efficacies. B-HT 933 produced a half-maximal response in canine saphenous vein at only 11% alpha 2-adrenoceptor occupancy, with a maximal response being obtained with 40-60% alpha 2-adrenoceptor occupancy. We conclude that the selective alpha 2-adrenoceptor agonist, B-HT 933, has high efficacy at alpha 2-adrenoceptors, such that a significant alpha 2-adrenoceptor reserve, or spare alpha 2-adrenoceptors, exists for this compound in canine saphenous vein.