Walsh S L, June H L, Schuh K J, Preston K L, Bigelow G E, Stitzer M L
Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Psychopharmacology (Berl). 1995 Jun;119(3):268-76. doi: 10.1007/BF02246290.
Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study characterized the agonist and antagonist effects of acute doses of buprenorphine and methadone in subjects maintained on either 30 (n = 7) or 60 (n = 6) mg/day oral methadone. Test doses of placebo [sl. and PO), methadone (15, 30, and 60 mg PO) and buprenorphine (2, 4, and 8 mg sl.) were administered to volunteers residing on a closed residential unit. Subjective, physiological, observer-rated, and cognitive/psychomotor measures were collected for 6.5 h after test doses. Test doses of methadone, but not buprenorphine, constricted pupils and produced dose-related increases on subjective report measures reflecting opioid agonist drug effects. Agonist effects of methadone were more prominent in the 30 mg than in the 60 mg methadone maintenance condition. Buprenorphine, but not methadone, precipitated opioid withdrawal signs and symptoms that were more prominent in the 60 mg than in the 30 mg methadone maintenance condition. These findings suggest that abrupt transition from methadone to buprenorphine may produce patient discomfort that is positively related to both methadone maintenance dose and buprenorphine transition dose.
丁丙诺啡是一种μ阿片受体部分激动剂，作为美沙酮维持治疗的替代药物，它正处于治疗阿片类药物依赖的试验阶段。本研究作为将患者从美沙酮治疗转换为丁丙诺啡治疗程序开发项目的一部分，考察了阿片类药物身体依赖程度与丁丙诺啡给药反应之间的关系。这项实验室研究对维持口服美沙酮剂量为30毫克（n = 7）或60毫克（n = 6）/天的受试者急性剂量丁丙诺啡和美沙酮的激动剂和拮抗剂作用进行了表征。向居住在封闭式住院单元的志愿者给予安慰剂（皮下注射和口服）、美沙酮（15、30和60毫克口服）和丁丙诺啡（2、4和8毫克皮下注射）的试验剂量。在给予试验剂量后6.5小时收集主观、生理、观察者评分以及认知/心理运动指标。试验剂量的美沙酮（而非丁丙诺啡）可使瞳孔收缩，并在反映阿片类激动剂药物作用的主观报告指标上产生剂量相关的增加。美沙酮的激动剂作用在30毫克美沙酮维持治疗组比60毫克美沙酮维持治疗组更显著。丁丙诺啡（而非美沙酮）引发了阿片类药物戒断体征和症状，在60毫克美沙酮维持治疗组比30毫克美沙酮维持治疗组更显著。这些发现表明，从美沙酮突然转换为丁丙诺啡可能会使患者产生不适，这种不适与美沙酮维持剂量和丁丙诺啡转换剂量均呈正相关。
