D2 receptor agonists and partial agonists: relationship between receptor binding measures and functional activity.

The neurotransmitter dopamine has been implicated in the aetiology of brain disorders such as Parkinson’s disease and schizophrenia, and dopamine receptors provide important targets for anti-parkinsonian and antipsychotic drugs. In particular, the beneficial use of dopamine D2 or DI/D2 agonists in the drug treatment of Parkinson’s disease is now well established [l], although the ideal agonist has not yet been identified. Alternative strategies for the treatment of this condition which are currently being evaluated include the use of D2 partial agonists alone or in combination with a full-efficacy DI agonist [2]. Another proposed therapeutic application for D2 receptor partial agonists is in the treatment of psychostimulant addiction [3]. Hence, elucidation of the molecular mechanisms underlying drug-receptor interaction and response and a simple procedure for predicting agonist intrinsic activity in vitm would facilitate the design and development of new agents with therapeutic potential.