New targets for antipsychotics.
Atypical antipsychotic drugs have a favorable side effect profile compared with older neuroleptics. Clozapine exhibits superior clinical efficacy in resistant schizophrenia. The neurochemical profile of these atypical agents suggests two distinct strategies in the development of novel antipsychotic drugs. Better-targeted dopaminergic agents may avoid the side effects associated with profound D2 receptor blockade. Current approaches include D3 receptor antagonists and drugs combining partial agonist activity at dopamine autoreceptors with conventional D2 antagonism. The D1 receptor may be a potential target for improving cognitive function in schizophrenia. Secondly drugs acting at glutamate (NMDA) and serotonin (5-HT(2A), 5-HT(1A), 5-HT(2C), 5-HT(3)) receptors may offer improved treatment particularly against resistant schizophrenic symptoms, as well as improving the side effect profile of antipsychotic drugs. This research in receptor pharmacology is set in the context of the increasingly recognised importance of the clinical care for patients with first onset schizophrenia and recent developments in pharmacogenomics.
Jones
Hugh M
HM
Section of Neurochemical Imaging, Institute of Psychiatry, Denmark Hill, London, SE5 8AF, UK.
Pilowsky
Lyn S
LS