Breslin D, Fields D W, Chou T C, Marion D N, Kane M, Vaughan E D, Felsen D
Department of Surgery/Division of Urology, New York Hospital-Cornell Medical Center, New York 10021.
J Urol. 1993 Feb;149(2):395-9. doi: 10.1016/s0022-5347(17)36102-5.
Medical management of benign prostatic hyperplasia (BPH) is an alternative to surgical treatment of this disease. A major target for pharmacologic therapy is the alpha-1 adrenergic receptor, since activation of this receptor by endogenous catecholamines is thought to contribute to outlet obstruction. In the present study, we compared the potency of various alpha-1 adrenergic antagonists against epinephrine-induced contraction of the canine prostate. The drugs tested were dibenzyline, prazosin, terazosin and YM617. The rank order of potency, comparing inhibitory constants (Ki's), was found to be YM617 >> prazosin > terazosin > dibenzyline. This study is the first to compare all of these drugs directly in the prostate in vivo. The rank order of potency of the drugs is similar to the rank order of potency at other alpha-1 receptors. These results demonstrate that 1) our model is useful in confirming activity of drugs at the alpha-1 receptor and 2) the prostate alpha-1 receptor is similar to other alpha-1 receptors. Whether activity at the alpha-1 adrenergic receptor is a sufficient determinant of clinical efficacy of these drugs remains to be determined.
良性前列腺增生（BPH）的药物治疗是该疾病手术治疗的一种替代方法。药物治疗的一个主要靶点是α-1肾上腺素能受体，因为内源性儿茶酚胺激活该受体被认为会导致出口梗阻。在本研究中，我们比较了各种α-1肾上腺素能拮抗剂对肾上腺素诱导的犬前列腺收缩的效力。所测试的药物有酚苄明、哌唑嗪、特拉唑嗪和YM617。比较抑制常数（Ki值）得出的效力顺序为YM617 >> 哌唑嗪 > 特拉唑嗪 > 酚苄明。本研究首次在体内前列腺中直接比较了所有这些药物。药物的效力顺序与在其他α-1受体上的效力顺序相似。这些结果表明：1）我们的模型有助于确认药物在α-1受体上的活性；2）前列腺α-1受体与其他α-1受体相似。这些药物在α-1肾上腺素能受体上的活性是否足以决定其临床疗效仍有待确定。
