Johnson J H, Rosecrans J A
J Pharmacol Exp Ther. 1980 Apr;213(1):110-3.
Morphine blocks ovulation in the rat and is associated with irregular menstrual cycles in humans. Methadone, the synthetic narcotic used to treat heroin addiction, was tested in rats for its ability to block ovulation. Equal doses of methadone were administered subcutaneously at 13:00, 14:00 and 15:00 hr on proestrus. Three different total (cumulative) doses were tested: 6, 9 and 15 mg/kg, in Wistar and Sprague-Dawley rats. The 6 mg/kg dose was ineffective, 9 mg/kg affected by Sprague-Dawley, whereas the 15 mg/kg dose blocked ovulation in both strains. Injection of saline at 13:00, 14:00 and 15:00 hr, or of the narcotic antagonist naltrexone at 12:00 had no effect on ovulation. Naltrexone prevented the blockade of ovulation by methadone, implicating narcotic receptors in the mediation of this action of methadone. Electrochemical stimulation of the medial preoptic area of the brain, or administration of exogenous luteinizing hormone overcame methadone's blockade of ovulation suggesting that the drug is acting via the central nervous system. The results of these studies suggest that menstrual dysfunction may not be a major problem in the clinical application of methadone.
吗啡可阻断大鼠排卵，且与人类月经周期不规律有关。美沙酮是用于治疗海洛因成瘾的合成麻醉药，研究人员在大鼠身上测试了其阻断排卵的能力。在动情前期的13:00、14:00和15:00皮下注射等量的美沙酮。对Wistar大鼠和Sprague-Dawley大鼠测试了三种不同的总（累积）剂量：6、9和15毫克/千克。6毫克/千克的剂量无效，9毫克/千克的剂量对Sprague-Dawley大鼠有影响，而15毫克/千克的剂量可阻断两种品系大鼠的排卵。在13:00、14:00和15:00注射生理盐水，或在12:00注射麻醉拮抗剂纳曲酮对排卵均无影响。纳曲酮可防止美沙酮对排卵的阻断，这表明麻醉受体参与了美沙酮这一作用的介导过程。对脑内侧视前区进行电化学刺激，或给予外源性促黄体生成素可克服美沙酮对排卵的阻断作用，这表明该药物是通过中枢神经系统发挥作用的。这些研究结果表明，月经功能障碍可能不是美沙酮临床应用中的主要问题。
