口服苯双甲吗啉对可卡因依赖个体的滥用可能性：对激动剂样替代疗法的启示。
Abuse Potential of Oral Phendimetrazine in Cocaine-dependent Individuals: Implications for Agonist-like Replacement Therapy.
作者信息
Bolin B Levi, Stoops William W, Sites Jeremy P, Rush Craig R
机构信息
Department of Behavioral Science (BLB, WWS, CRR), University of Kentucky College of Medicine, 140 Medical Behavioral Science Building, Lexington, KY; Department of Psychology (WWS, CRR), University of Kentucky College of Arts and Sciences, 110 Kastle Hall, Lexington, KY; Department of Psychiatry (WWS, CRR), University of Kentucky College of Medicine, 3470 Blazer Parkway, Lexington, KY; and University of Kentucky College of Medicine (JPS), 138 Leader Avenue, Lexington, KY.
出版信息
J Addict Med. 2016 May-Jun;10(3):156-65. doi: 10.1097/ADM.0000000000000206.
OBJECTIVES
Phendimetrazine is a prodrug for the monoamine releaser phenmetrazine-a drug with known abuse potential. Preclinical studies suggest that phendimetrazine has limited abuse potential and may have promise as an agonist-like replacement therapy for cocaine dependence. This study evaluated the abuse potential of phendimetrazine in humans.
METHODS
Nine cocaine-dependent individuals (N = 9) were enrolled to investigate the abuse potential of phendimetrazine and d-amphetamine, using a double-blind, placebo-controlled, within-subject design. Subjective and cardiovascular effects of oral phendimetrazine (35, 70, and 105 mg), d-amphetamine (10, 20, and 30 mg), and placebo were assessed in quasi-random order across 8 sessions lasting for approximately 8 hours each.
RESULTS
d-Amphetamine (20 and 30 mg) significantly increased cardiovascular measures in a time and dose-related manner, but phendimetrazine did not systematically alter cardiovascular measures. Although d-amphetamine and phendimetrazine significantly increased ratings indicative of abuse potential (eg, drug liking) and stimulant-like effects relative to placebo, these increases were generally small in magnitude, with phendimetrazine producing significant effects on fewer abuse-related measures and at fewer time points than d-amphetamine.
CONCLUSIONS
These preliminary findings suggest that oral phendimetrazine and d-amphetamine may have limited abuse potential in cocaine-dependent individuals. These findings collectively emphasize that the clinical utility of medications to treat cocaine-use disorders should be weighed carefully against their potential for abuse and diversion, with careful attention paid to evaluating abuse potential in a clinically relevant population of interest. Future studies are needed to further elucidate the potential utility of phendimetrazine as an agonist-like replacement therapy for cocaine dependence.
目的
苯双甲吗啉是单胺释放剂苯甲吗啉的前体药物，苯甲吗啉是一种已知具有滥用潜力的药物。临床前研究表明，苯双甲吗啉的滥用潜力有限，可能有望作为可卡因依赖的激动剂样替代疗法。本研究评估了苯双甲吗啉在人体中的滥用潜力。
方法
招募了9名可卡因依赖个体（N = 9），采用双盲、安慰剂对照、受试者内设计，研究苯双甲吗啉和右旋苯丙胺的滥用潜力。口服苯双甲吗啉（35、70和105毫克）、右旋苯丙胺（10、20和30毫克）和安慰剂的主观和心血管效应在8个疗程中按准随机顺序进行评估，每个疗程持续约8小时。
结果
右旋苯丙胺（20和30毫克）以时间和剂量相关的方式显著增加了心血管指标，但苯双甲吗啉并未系统性地改变心血管指标。尽管相对于安慰剂，右旋苯丙胺和苯双甲吗啉显著增加了表明滥用潜力的评分（如对药物的喜好）和类似兴奋剂的效应，但这些增加的幅度通常较小，与右旋苯丙胺相比，苯双甲吗啉对较少的与滥用相关的指标产生显著影响，且在较少的时间点产生影响。
结论
这些初步研究结果表明，口服苯双甲吗啉和右旋苯丙胺在可卡因依赖个体中的滥用潜力可能有限。这些研究结果共同强调，治疗可卡因使用障碍药物的临床效用应与其滥用和转移的可能性进行仔细权衡，同时要特别注意在临床相关的目标人群中评估滥用潜力。未来需要进一步研究以阐明苯双甲吗啉作为可卡因依赖的激动剂样替代疗法的潜在效用。
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