Antibody Medications For (+) Meth Dependence

University Of Arkansas Med Scis Ltl Rock, Little Rock AR

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Abstract

Methamphetamine [(+)]methamphetamine, or (+)METH] has been a serious drug problem in the United States since the middle 1980s. It is by far the most prevalent synthetic controlled substance clandestine manufactured in the United States and it is abused throughout the world. Although there has been good success in the development of therapeutic drugs to treat some types of drug abuse, at this time there is no pharmacological treatment of (+)METH abuse that has clinical acceptance. This project will use antibody-based therapies as "pharmacological antagonists" of (+)METH abuse. (+)METH abuse will be studied using two animal models, drug self-administration and drug discrimination. Drug self-administration is generally considered to be a model of the reinforcing properties of (+)METH and drug discrimination is considered to be a model of some of the subjective effects of (+)METH and drug discrimination is considered to be a model of some of the subjective effects of (+)METH that presumably contribute to its abuse. Anti-(+)METH antibodies will be screened for their ability to reduce (+)METH self-administration and to block the discriminative stimulus effects of (+)METH in rats. The most promising antibodies will be subjected to more rigorous testing to determine dose-response relationships, duration of action, specificity for blocking the effects of other (+)METH-like drugs, ability to prevent relapse to (+) METH abuse, and interaction with behavioral treatments for (+)METH abuse. Experiments on the effects of the most promising anti-(+)METH antibody on (+)METH self administration will be repeated in squirrel monkeys to develop a preclinical data base for the testing of these antibodies as pharmacotherapy for (+)METH abuse in humans.