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Pharmacological blocking agents are an important treatment approach for the current epidemic of drug abuse. This approach is multidisciplinary, ranging from molecular neuroscience for developing these blocking agents to behavioral therapies for establishing treatment delivery systems. This paper outlines the biological, behavioral, and clinical components of the pharmacological blocking agent approach. Clinical results using two blocking agents, naltrexone for opioid abuse and disulfiram for alcohol abuse, are reviewed as a source of leads in developing potential agents for treating sedative and stimulant abuse. While specific pharmacological antagonists have been developed for benzodiazepines, such agents are not yet available for stimulants. Furthermore, the clinical utility of stimulant antagonists may depend on the development of multisite agents that partially block several neurotransmitter systems rather than target a single-system brain receptor.

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