Pinelli A, Trivulzio S, Tomasoni L
Department of Pharmacology, Chemotherapy and Medical Toxicology, Milan, Italy.
Eur J Pharmacol. 1997 Dec 11;340(2-3):111-9. doi: 10.1016/s0014-2999(97)01349-6.
This study tested whether a 5-HT3 receptor antagonist could reverse the signs of precipitated opioid withdrawal. Rats were treated with either saline or morphine for 4 days. After the four days, half of the rats in each group received naloxone and half received saline. Each animal also received one of four doses of ondansetron (0, 1, 2 and 4 mg/kg i.p.). Administration of ondansetron to rats receiving naloxone after chronic morphine decreased the intensity of withdrawal signs such as increased defecation, jumping and wet-dog shakes, elevated the nociceptive threshold values which were decreased by precipitated withdrawal, but produced no change in urination, rectal temperature or salivation. The effects exhibited by ondansetron administration may be explained through interference of its 5-HT3 receptor antagonist activity with serotoninergic mechanisms involved in the regulation of these withdrawal symptoms. The use of this drug is thus suggested as a possible treatment of opioid withdrawal signs in heroin addicts.
本研究测试了5-羟色胺3（5-HT3）受体拮抗剂是否能够逆转阿片类药物戒断反应的体征。大鼠连续4天接受生理盐水或吗啡处理。4天后，每组一半的大鼠接受纳洛酮，另一半接受生理盐水。每只动物还接受四种剂量（0、1、2和4毫克/千克腹腔注射）的昂丹司琼中的一种。对长期使用吗啡后接受纳洛酮的大鼠给予昂丹司琼，可降低戒断反应体征的强度，如排便增加、跳跃和湿狗样抖动，提高因戒断反应而降低的痛觉阈值，但对排尿、直肠温度或唾液分泌没有影响。昂丹司琼给药所表现出的效果可能是由于其5-HT3受体拮抗剂活性干扰了参与调节这些戒断症状的5-羟色胺能机制。因此，建议使用这种药物作为海洛因成瘾者阿片类药物戒断体征的一种可能治疗方法。
