Alpha 2-adrenoceptor antagonists: effects on ejaculation, penile erection and pelvic thrusting behavior in dogs.
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.
Yonezawa
A
A
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan. yonezawa@tohoku-pharm.ac.jp
Ando
R
R
Watanabe
C
C
Furuta
S
S
Kutsuwa
M
M
Sakurada
S
S
Kimura
Y
Y
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D004285:Dogs; D004542:Ejaculation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010388:Pelvis / Q000502:physiology; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology
D018674:Adrenergic Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2