Novel pharmacotherapies for cocaine abuse 1997-2000

The discovery of a pharmacotherapeutic treatment for cocaine at,use and add iction has been a research target that has received much attention in the p ast three years. Since the patent literature on this topic was last reviewe d [1], major advances have been made in the understanding of the neurochemi cal basis of cocaine addiction. State of the art technologies have aided th e characterisation of mechanistic targets of cocaine. For example, the deve lopment of transgenic mice and the use of PET imaging to visualise cocaine binding sites in the human brain are exciting new advances that have comple mented the more well-established pharmacological paradigms such as radiolig and binding assays and animal models of cocaine abuse. In addition, classic al and computer-aided drug design has yielded highly potent and selective l igands to target relevant neurochemical substrates and provide valuable inf ormation on the role these substrates play in pharmacological actions of co caine. 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 ha ve then been utilised to predict the efficacy of these agents. Although an efficacious medication for treating cocaine abuse in humans is vet to be id entified, numerous candidates are being evaluated in advanced preclinical s tudies and several agents have reached the clinical trial stage. This artic le reviews the research advances published in the patent literature from Ja nuary 1997 through December 1999, supplemented with selected peer-reviewed literature on the design and development of novel agents for the treatment of cocaine abuse.