Yonezawa A, Ando R, Watanabe C, Furuta S, Kutsuwa M, Sakurada S, Kimura Y
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
Pharmacol Biochem Behav. 2001 Sep;70(1):141-7. doi: 10.1016/s0091-3057(01)00584-6.
We previously reported that systemic administration of yohimbine, an alpha2-adrenoceptor antagonist, exerts a biphasic effect (stimulating and suppressing) on ejaculation in dogs, when this function is analyzed using the amount of ejaculated semen in response to genital stimulation. To clarify the effect of alpha2-adrenoceptor blockade on male sexual function, we investigated the effects of four selective alpha2-adrenoceptor antagonists, rauwolscine, idazoxan, RX821002 and mydaglizole, on sexual responses (ejaculation, penile erection and pelvic thrusting behavior) elicited by manual penile stimulation in dogs. Rauwolscine (intraperitoneal, 30 min before the testing) caused a biphasic effect on ejaculation; the amount of ejaculated semen produced by the stimulation was significantly increased by the lower doses (0.1 and 0.3 mg/kg), whereas it was decreased by the higher doses (1.0 and 2.0 mg/kg). The higher doses of rauwolscine also markedly inhibited both penile erection and pelvic thrusting behavior. Idazoxan and RX821002, at doses of 0.1 and 0.3 mg/kg, caused a significant increase in the amount of ejaculated semen without affecting other sexual functions. RX821002 (2.0 mg/kg), but not idazoxan (2.0 mg/kg), moderately inhibited both penile erection and pelvic thrusting behavior. Mydaglizole, a peripherally acting alpha2-adrenoceptor antagonist, did not affect the sexual responses at any doses (0.1-4.0 mg/kg). In the ejaculatory declining test, all alpha2-adrenoceptor antagonists (0.1 mg/kg), except for mydaglizole, completely prevented the decrease in ejaculatory capacity produced by antecedent ejaculation. These results indicate that, though the range of the effective dose is narrow, the alpha2-adrenoceptor antagonists that can block the central alpha2-adrenoceptors have the stimulatory effects on ejaculatory function. The difference of the sexual effects may be based on the action except for the alpha2-adrenoceptor blockade.
我们之前报道过,当使用对生殖器刺激的射精精液量来分析射精功能时,α2肾上腺素能受体拮抗剂育亨宾的全身给药对犬的射精产生双相作用(刺激和抑制)。为了阐明α2肾上腺素能受体阻断对男性性功能的影响,我们研究了四种选择性α2肾上腺素能受体拮抗剂,萝芙辛、咪唑克生、RX821002和米达格列唑,对犬手动阴茎刺激引发的性反应(射精、阴茎勃起和盆腔推力行为)的影响。萝芙辛(腹腔注射,测试前30分钟)对射精产生双相作用;较低剂量(0.1和0.3毫克/千克)刺激产生的射精精液量显著增加,而较高剂量(1.0和2.0毫克/千克)则使其减少。较高剂量的萝芙辛也显著抑制阴茎勃起和盆腔推力行为。咪唑克生和RX821002,剂量为0.1和0.3毫克/千克时,射精精液量显著增加,而不影响其他性功能。RX821002(2.0毫克/千克),但不是咪唑克生(2.0毫克/千克),适度抑制阴茎勃起和盆腔推力行为。外周作用的α2肾上腺素能受体拮抗剂米达格列唑在任何剂量(0.1 - 4.0毫克/千克)下均不影响性反应。在射精能力下降试验中,除米达格列唑外,所有α2肾上腺素能受体拮抗剂(0.1毫克/千克)均完全阻止了先前射精导致的射精能力下降。这些结果表明,尽管有效剂量范围较窄,但能够阻断中枢α2肾上腺素能受体的α2肾上腺素能受体拮抗剂对射精功能具有刺激作用。性效应的差异可能基于α2肾上腺素能受体阻断以外的作用。