Balster R L
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
Br J Addict. 1991 Dec;86(12):1549-58. doi: 10.1111/j.1360-0443.1991.tb01747.x.
Animal laboratory studies can provide useful information concerning the potential of drugs for abuse. Over the past 50 years, methods have been developed for use with animal subjects which allow the evaluation of pharmacological properties of drugs which are particularly relevant to their abuse. The methods for preclinical drug abuse liability testing are reviewed under six heading: (1) establishment of the degree of pharmacological equivalence to known drugs of abuse, (2) drug discrimination studies, (3) tests of tolerance and cross-tolerance, (4) tests of physical dependence capacity, (5) drug self-administration tests of reinforcing effects, and (6) evaluation of toxicity and performance impairment at self-administered doses. Preclinical studies can be helpful early in drug development to select lead compounds with low abuse potential for further study. In the case of new or already marketed medications, animal testing can often compliment and extend abuse liability evaluation in human subjects. The results of abuse potential evaluation studies can be useful in making decisions about the possible need for regulation under national and international drug laws, and thus play an important role in drug abuse prevention.
动物实验室研究能够提供有关药物滥用潜力的有用信息。在过去50年里,已开发出适用于动物实验对象的方法,这些方法可用于评估与药物滥用特别相关的药理学特性。临床前药物滥用可能性测试方法分为六个类别进行综述:(1)确定与已知滥用药物的药理学等效程度;(2)药物辨别研究;(3)耐受性和交叉耐受性测试;(4)身体依赖性能力测试;(5)药物自我给药强化效应测试;(6)对自我给药剂量下的毒性和行为能力损害进行评估。临床前研究在药物研发早期有助于筛选出滥用潜力低的先导化合物,以供进一步研究。对于新药物或已上市药物,动物试验通常可以补充并扩展对人体滥用可能性的评估。滥用潜力评估研究的结果有助于依据国家和国际药品法律,决定是否可能需要进行监管,从而在预防药物滥用方面发挥重要作用。