Affinity of the miotic drug, dapiprazole, at alpha 1-adrenoceptor subtypes A, B and D.
The functional affinities of the alpha 1-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 alpha 1-adrenoceptor subtype-discriminating antagonists. Dapiprazole had relatively high affinity both at rat vas deferens alpha 1A-adrenoceptors (pA2 = 7.93) and at rat aortic alpha 1D-adrenoceptors (pA2 = 8.26), whereas its affinity at guinea-pig splenic alpha 1B-adrenoceptors (pA2 = 7.13) was lower. The reference antagonists, 5-methylurapidil and the 5-methylurapidil/flesinoxan 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 diHCI) were confirmed as selective for the B and D subtypes of alpha 1-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 alpha 1-adrenoceptors; the possible therapeutic consequence of this is discussed.
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D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D006168:Guinea Pigs; D008297:Male; D008916:Miotics / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010879:Piperazines; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism*; D014649:Vas Deferens / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D008916:Miotics; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D014230:Triazoles; C035289:dapiprazole; D009638:Norepinephrine