Elsevier

Life Sciences

Volume 50, Issue 2, 1992, Pages 127-135
Life Sciences

Binding characteristics of naftopidil and α1-adrenoceptor antagonists to prostatic α-adrenoceptors in benign prostatic hypertrophy

https://doi.org/10.1016/0024-3205(92)90294-YGet rights and content

Abstract

Binding properties of naftopidil and α1-adrenoceptor antagonists to α-adrenoceptors in prostates from benign prostatic hypertrophy (BPH) were characterized by radioreceptor assays usinh [3H]prazosin and [3]- rauwolscine. Specific binding of [3H]prazosin and [3H] rauwolscine in human prostatic membranes was saturable and of high affinity, and it showed a pharmacological specificiwhich characterized α1 and α2- adrenoceptors, respectively. Naftopidil and several α1 antagonists competed for prostatic [3H]prazosin binding in order: R-(-)-YM-12617 >prazosin>bonazosin>terazosin>naftopidil>urapidil, and the inhibitory effect (Ki = 11.6 nM) of naftopidil was 10 to 45 times less potent than quinazoline derivatives such as prazosin, bunazosin and terazosin. The potencies of these antagonists in competing for [3H]prazosin binding sites in human prostates correlated well with their pharmacological potencies (pA2). Scatchard analysis indicated that the decrease of prostatic [3H]prazosin binding by naftopidil was due to a marked increase in the Kd value without a change in the Bmax value. The inhibition of prostatic [3H]prazosin binding by naftopidil was reversible. Naftopidil also inhibited prostatic [3H]rauwolscine binding (Ki = 70.0 nM). Thus, it is suggested that naftopidil antagonizes α1-adrenoceptors in human prostates in a competitive and reversible manner.

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