Affinity of the Miotic Drug, Dapiprazole, at α1-Adrenoceptor Subtypes A, B and D

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Abstract
The functional affinities of the α1-adrenoceptor antagonist, dapiprazole, currently being used to reverse diagnostic pupillary dilation, were determined at subtype A in rat vas deferens, at subtype B in guinea-pig spleen and at subtype D in rat aorta and compared with various α1-adrenoceptor subtype-discriminating antagonists. Dapiprazole had relatively high affinity both at rat vas deferens α1A-adrenoceptors (pA2 = 7.93) and at rat aortic α1D-adrenoceptors (pA2 = 8.26), whereas its affinity at guinea-pig splenic α1B-adrenoceptors (pA2 = 7.13) was lower. The reference antagonists, 5-methylurapidil and the 5-methylurapidil/fiesinoxan hybrid, B8805–033((±)-1,3,5-trimethyl-6[[3[4(2(2,3-dihydro-2-hydroxymethyl)-1,4-benzodioxin-5-yl)-1-piperazinyl]propyl]-amino]2,4(1H,3H)-pyrimidinedione), were 40- and 1500-fold selective for the A subtype, whereas spiperone and BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione diHCl) were confirmed as selective for the B and D subtypes of α1-adrenoceptors, respectively. Thus, in functional experiments dapiprazole seems to be moderately selective (approximately 10-fold) for the A and D over the B subtype of α1-adrenoceptors; the possible therapeutic consequence of this is discussed.