Discovery and development of novel agents to treat drug abuse

Abstract

The use of psychoactive plants is an almost universal occurrence in human culture. Information about the pharmacological effects of psychoactive substances has been passed down for generations and much of what we know about the function, structure, and components of the central nervous system (CNS) is the direct result of studying psychoactive active natural products. Unfortunately the abuse of psychoactive natural products has profound effects on human health. For example, the abuse of cocaine and other CNS stimulants is associated with substantial neuropsychiatric morbidity, as well as, enhancing transmission of HIV-1, hepatitis B and C, and drug resistant tuberculosis. Presently, there are no FDA approved treatments for CNS stimulant abuse. A growing body of evidence indicates that κ opioid receptors may be involved in the modulation of some of the abuse related effects of psychostimulants. Notably, repeated or chronic psychostimulant administration results in a prolonged upregulation of the κ receptor/dynorphin system. The κ receptor/dynorphin system is thought to be part of the brain's counter-regulatory response to enhanced dopaminergic acitivity, which is thought to be a major initial event underlying psychostimulant-induced reinforcement and abuse potential. This talk will detail our recent progress in a program directed toward identifying novel compounds to treat drug dependence by targeting κ opioid receptors.