Inverse agonism of the antipsychotic drugs at the D-2 dopamine receptor

Strange, P. G. (2003) Inverse agonism of the antipsychotic drugs at the D-2 dopamine receptor. In: Ijzerman, A. P. (ed.) Inverse Agonism. International Congress Series, 1249. Elsevier Science Bv, Amsterdam, pp. 153-162. ISBN 044451032X doi: 10.1016/s0531-5131(03)00607-1

Abstract/Summary

The antipsychotic drugs had been assumed to act as antagonists at D-2 dopamine receptors but recently these drugs have been shown to possess inverse agonist properties at this receptor. Inverse agonism may be demonstrated from the ability of these drugs to potentiate forskolin-stimulated cAMP accumulation or to suppress agonist-independent [S-35]GTPgammaS binding. The antipsychotic drugs tested generally appear as full inverse agonists in these assays regardless of chemical or therapeutic class. The mechanism of inverse agonism of the antipsychotic drugs is still unclear but may involve stabilisation of the ground state of the D-2 receptor. (C) 2003 Elsevier Science B.V All rights reserved.