The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter

被引:19
作者
Izenwasser, S [1 ]
Newman, AH [1 ]
Cox, BM [1 ]
Katz, JL [1 ]
机构
[1] UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814
基金
美国国家卫生研究院;
关键词
dopamine transporter; cocaine; meperidine;
D O I
10.1016/0014-2999(95)00696-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Meperidine has atypical opioid receptor agonist effects and shares some structural features with the phenyltropane (WIN) analogs of cocaine. In combination with 0.1 mg/kg naltrexone, meperidine produced cocaine-like discriminative stimulus effects in monkeys, whereas morphine was inactive. Both cocaine and meperidine inhibited [H-3]dopamine uptake in chopped rat caudate putamen with comparable potencies; meperidine differed from cocaine in that its effects could be characterized as having predominantly a single high-affinity component. Morphine was not active in inhibiting [H-3]dopamine uptake, indicating that the effect of meperidine was not via a classic mu-opioid receptor agonist action. Further, meperidine but not morphine displaced [H-3]WIN 35,428 (2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane) binding. These data suggest that the actions of meperidine that are atypical of opioids are due to activity at the dopamine transporter. In addition, meperidine appears to interact predominantly with the high-affinity component of the dopamine transporter, and this high-affinity component may be the site of importance for the production of cocaine's behavioral effects.
引用
收藏
页码:9 / 17
页数:9
相关论文
共 44 条
[1]  
Andrews HL, 1942, J PHARMACOL EXP THER, V76, P89
[2]  
BARRETT JE, 1974, J PHARMACOL EXP THER, V196, P605
[3]   DISCRIMINATIVE STIMULUS EFFECTS OF CYCLORPHAN - SELECTIVE ANTAGONISM WITH NALTREXONE [J].
BERTALMIO, AJ ;
WOODS, JH .
PSYCHOPHARMACOLOGY, 1992, 106 (02) :189-194
[4]   NEW, POTENT COCAINE ANALOGS - LIGAND-BINDING AND TRANSPORT STUDIES IN RAT STRIATUM [J].
BOJA, JW ;
CARROLL, FI ;
RAHMAN, MA ;
PHILIP, A ;
LEWIN, AH ;
KUHAR, MJ .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 184 (2-3) :329-332
[5]   [H-3] COCAINE BINDING AND INHIBITION OF [H-3] DOPAMINE UPTAKE IS SIMILAR IN BOTH THE RAT STRIATUM AND NUCLEUS ACCUMBENS [J].
BOJA, JW ;
KUHAR, MJ .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 173 (2-3) :215-217
[6]   CENTRAL AND PERIPHERAL MONOAMINERGIC MEMBRANE-PUMP BLOCKADE BY SOME ADDICTIVE ANALGESICS AND ANTIHISTAMINES [J].
CARLSSON, A ;
LINDQVIST, M .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1969, 21 (07) :460-+
[7]   COCAINE RECEPTOR - BIOCHEMICAL-CHARACTERIZATION AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF COCAINE ANALOGS AT THE DOPAMINE TRANSPORTER [J].
CARROLL, FI ;
LEWIN, AH ;
BOJA, JW ;
KUHAR, MJ .
JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (06) :969-981
[8]  
COOK L, 1992, SOC NEUR ABSTR, V18, P230
[9]   QUANTITATIVE STUDIES OF ANTAGONISM BY NALORPHINE OF SOME OF ACTIONS OF MORPHINE-LIKE ANALGESIC DRUGS [J].
COX, BM ;
WEINSTOCK, M .
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, 1964, 22 (02) :289-&
[10]   ROLE OF 5-HYDROXYTRYPTAMINE AND NORADRENALINE IN HYPERTHERMIC REACTION INDUCED BY PETHIDINE IN RABBITS PRETREATED WITH PARGYLINE [J].
FAHIM, I ;
ISMAIL, M ;
OSMAN, OH .
BRITISH JOURNAL OF PHARMACOLOGY, 1972, 46 (03) :416-&