Koyuncuoğlu H, Saydam B
Istanbul Medical Faculty, Department of Pharmacology and Clinical Pharmacology, Turkey.
Int J Clin Pharmacol Ther Toxicol. 1990 Apr;28(4):147-52.
According to the hypothesis that the development of physical dependence on and tolerance to opiates depends on the inhibition by opiates of L-asparaginase and L-glutaminase activities in the brain, and the blockade by opiates of the aspartatergic/glutamatergic receptors especially NMDA, four female and fourty-four male heroin addicts were included in a double-blind clinical trial. Four mg chlorpromazine (CPZ) was administered every hour and 10 mg diazepam (DIA) every 6 hours to a group consisting of two female and nineteen male inpatients. The remaining subjects received 15 mg non-opioid antitussive dextromethorphan (DM) instead of CPZ. The withdrawn addicts were controlled twice a day and yawning, lacrimation, rhinorrhoea, perspiration, goose flesh, muscle tremor, dilated pupils, anorexia, joint and muscle aches, restlessness, insomnia, emesis, diarrhea, craving and rejection of smoking as abstinence syndrome signs were observed and rated on a scale of 1, 2 and 3 points according to their intensity. All signs, except perspiration and emesis, were significantly less intense in the group given DM + DIA than CPZ + DIA. The other plus points included the immediate stop of craving and the early onset of smoking in DM + DIA group. The results are considered to be supporting evidence for the hypothesis emphasizing the blockade of NMDA receptors by opiates in opiate addiction. Furthermore, the decrease caused by non-opioid NMDA antagonists in the responsiveness of NMDA receptors appears very promising for the treatment of opiate addicts.
根据以下假说,即对阿片类药物产生身体依赖性和耐受性的发展取决于阿片类药物对大脑中L - 天冬酰胺酶和L - 谷氨酰胺酶活性的抑制作用,以及阿片类药物对天冬氨酸能/谷氨酸能受体尤其是NMDA受体的阻断作用,4名女性和44名男性海洛因成瘾者被纳入一项双盲临床试验。每小时给由2名女性和19名男性住院患者组成的一组服用4毫克氯丙嗪(CPZ),每6小时服用10毫克地西泮(DIA)。其余受试者服用15毫克非阿片类镇咳药右美沙芬(DM)替代CPZ。对戒断的成瘾者每天进行两次检查,观察呵欠、流泪、流涕、出汗、鸡皮疙瘩、肌肉震颤、瞳孔散大、厌食、关节和肌肉疼痛、烦躁不安、失眠、呕吐、腹泻、渴求以及对吸烟的抗拒等戒断综合征体征,并根据其强度按1、2、3分进行评分。除出汗和呕吐外,服用DM + DIA组的所有体征的强度均明显低于CPZ + DIA组。其他优点包括DM + DIA组中渴求立即停止以及吸烟提前开始。这些结果被认为是支持强调阿片类药物在阿片类成瘾中对NMDA受体阻断作用这一假说的证据。此外,非阿片类NMDA拮抗剂导致NMDA受体反应性降低,这对于治疗阿片类成瘾者似乎非常有前景。