Effect of KMD-3213, a novel α_1 -adrenoceptor (AR) antagonist, on the blood pressure response to tilting in rats

• Published in: Japanese Journal of Pharmacology Vol. 71; no. suppl.2; p. 329
• Main Authors: Masachiyo Hora, Ryoichi Yamagishi, Katsuyosi Akiyama, Makio Kitazawa, Arao Ujiie
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 1996
• ISSN: 0021-5198; 1347-3506

KMD-3213, a novel α_1 -AR antagonist, is developed for treatment of urinary outlet obstruction associated with the benign prostatic hyperplasia. We previously reported that KMD-3213 has equal potency to suppress urethral pressure to Tamsulosin(Tam) hut has much less effect on blood pressure than Tam in rats. In the present study, we examined the effect of KMD-3213 on orthostatic hypotension that is a sick effect induced by α_1 -AR antagonists for treatment of urinary outlet obstruction and compared that effect with Tam and Prazosin(Pz). Male Sprague-Dawley rats were anesthetized with the mixture of urethane, α-chloralose and pentobarbital intravenously and were fixed in a supine position on boards. In tilt experiments (tests of orthostatic hypotension), animals were tilted by 45℃ head up position for 2 min, and the blood pressure response was measured continuously. Drugs were injected intravenously 3 min before the tilting, and inhibitory effects of the chugs on the response during the tilting were examined. After tilting, blood pressure fell sharply. In the control experiments, the blood pressure immediately returned to the normal level and was stable during the tilting. KMD-3213, Tam and Pz inhibited the blood pressure response to tilting in dose-dependent manner. Ten μg/kg of Tam and Pz completely inhibited the response, whereas 7.5 μg/kg of KMD-3213 had no effect. Two hunched thirty μg/kg of KMD-3213 completely inhibited it. The results indicate that inhibitory effects of KMD-3213 on the blood pressure response is 20 times lower than those of Tam or Pz. It is expected that KMD-3213 causes remarkably less orthostatic hypotension than Tam or Pz.