Novel pharmacotherapies for cocaine abuse 1997-2000

The discovery of a pharmacotherapeutic treatment for cocaine at,use and addiction has been a research target that has received much attention in the past three years. Since the patent literature on this topic was last reviewed [1], major advances have been made in the understanding of the neurochemical basis of cocaine addiction. State of the art technologies have aided the characterisation of mechanistic targets of cocaine. For example, the development of transgenic mice and the use of PET imaging to visualise cocaine binding sites in the human brain are exciting new advances that have complemented the more well-established pharmacological paradigms such as radioligand binding assays and animal models of cocaine abuse. In addition, classical and computer-aided drug design has yielded highly potent and selective ligands to target relevant neurochemical substrates and provide valuable information on the role these substrates play in pharmacological actions of cocaine. These advances have opened the door to the discovery of novel agents that selectively interact at various neurotransmitter and receptor systems relevant to cocaine's addictive effects. Animal models of cocaine abuse have then been utilised to predict the efficacy of these agents. Although an efficacious medication for treating cocaine abuse in humans is vet to be identified, numerous candidates are being evaluated in advanced preclinical studies and several agents have reached the clinical trial stage. This article reviews the research advances published in the patent literature from January 1997 through December 1999, supplemented with selected peer-reviewed literature on the design and development of novel agents for the treatment of cocaine abuse.