Dopamine D₃agonists

Abstract

The dopamine D₃ receptor is predominantly expressed in limbic regions of the brain, such as the nucleus accumbens, island of Calleja and hippocampus, and is known to be associated with cognitive and emotional functions. This neuroanatomical distribution suggests that D₃ receptors may be important targets for the development of therapeutic treatments for schizophrenia and drug abuse. Several new compounds have been reported to display a greater selectivity for D₃ receptors than D₂ receptors. For instance, both PD 128907 and 7-OH-DPAT were characterised as D₃ preferring receptor agonists in both binding and cellular studies, with the former compound being the most selective. Recent studies have suggested that the D₃ receptor subtype plays a pivotal role in the reinforcing effects of cocaine. The D₃ receptor may thus be a useful target for drug development of anticocaine medications. However, therapies based on mimicking the acute effects of abused drugs may be ineffective on compulsive drug-seeking, drug craving and relapse, which are the common critical problems in the treatment of drug addiction. Hence, liability for dependence on dopamine D₃ receptor agonists is a risk to be taken into consideration. The close association of the D₃ receptor with mesolimbic dopaminergic circuits suggests that partial blockade of the D₃ receptor may selectively decrease the rewarding effects of cocaine without contributing to the dysphoria associated with cocaine withdrawal. The selective and partial D₃ receptor agonist BP 897 has the unprecedented property of reducing cocaine-seeking behaviour maintained by a cocaine-associated cue. Compounds like BP 897 could be useful for reducing relapse vulnerability, with minimal liability of dependence. A review of recent patents of the dopamine agonists in the last four years suggest some potential therapeutic benefits from this class of drugs to treat psychiatric and neurologic diseases. It also outlines the utility of dopamine agonists in various new indications.

• cocaine addiction
• dopamine agonist
• pramipexole