Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys
Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys
复制标题
DOI：
10.1016/j.drugalcdep.2013.05.005
复制
发表时间：
2013-08-01
影响因子：
4.2
通讯作者：
Negus, S. Stevens
中科院分区：
文献类型：
--
作者：
Banks, Matthew L.;Blough, Bruce E.;Negus, S. Stevens
背景资料：单胺释放剂如苯甲曲嗪或d-苯丙胺作为可卡因依赖的候选激动剂药物的临床效用受到其高滥用倾向的阻碍。苯甲曲嗪是一种临床上可获得的III类厌食剂，其用作苯甲曲嗪的前药，因此可能具有较低的滥用倾向。本研究确定了连续14天的治疗与苯甲曲嗪对可卡因与食物的选择在恒河猴（N=4）的影响：响应下维持一个并行的时间表的食物交付（1克丸，固定比例100计划）和可卡因注射（0-0.1毫克/公斤/注射，固定比例10计划）。在连续静脉注射生理盐水或（+）-苯甲曲嗪（0.32-1.0 mg/kg/h）之前和14天期间，每天测定剂量-效应曲线。（+）-苯甲曲嗪14天治疗的效果（0.1-0.32 mg/kg/h; N=5）和d-苯丙胺（0.032-0.1 mg/kg/h; N=6）进行比较。结果：在生理盐水治疗期间，食物主要是在低可卡因剂量可用期间选择的（0、0.0032和0.01 mg/kg/注射），可卡因主要在较高可卡因剂量（0.032和0.1 mg/kg/注射）可用期间选择。苯甲曲嗪最初降低总体反应，而不显着改变可卡因的选择。在14天的过程中，耐受性发展到速率降低效应，苯甲曲嗪剂量依赖性地减少可卡因选择（在0.032 mg/kg/注射可卡因时显著）。Phenmetrazine和D-苯丙胺产生定性相似的effects.Conclusions：这些结果表明，苯甲曲嗪可以产生显着的，虽然温和，减少可卡因的选择在恒河猴。苯甲曲嗪可能是特别适合作为候选药物的人类研究，因为其附表III的临床可用性。(C)2013爱思唯尔爱尔兰有限公司保留所有权利。
Background: The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with phendimetrazine on cocaine vs. food choice in rhesus monkeys (N=4).Methods: Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0-0.1 mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose-effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-phendimetrazine (0.32-1.0 mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1-0.32 mg/kg/h; N=5) and d-amphetamine (0.032-0.1 mg/kg/h; N=6) were also examined for comparison.Results: During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1 mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects.Conclusions: These results demonstrate that phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability. (C) 2013 Elsevier Ireland Ltd. All rights reserved.