Novel research strategies in the pharmacology of schizophrenia

Currently available drugs to treat schizophrenia prove to be only partially effective and often produce disturbing side effects. Because pathophysiological mechanisms underlying schizophrenia are unclear, and animal models with construct validity virtually do not exist, pharmaceutical research faces considerable difficulties in its attempt to develop more effective drugs to treat this disorder. Recent findings reviewed in this article about differences in the mode of action between typical and atypical neuroleptic drugs may provide some clues about the disease itself and about potential new therapies. The discovery of novel dopamine receptor subtypes as potential targets for the antipsychotic action may offer new possibilities for pharmaceutical industry. Glutamatergic AMPA receptors seem to be another important potential site of action for novel antischizophrenic drugs, in particular those targeting negative symptoms. Findings from studies on the effects of chronic treatment with typical and atypical drugs on postreceptor intracellular processes, such as expression of genes encoding transcription factors or their target genes, may elucidate mechanisms by which these drugs exert their therapeutic action. Finally, novel animal models with construct and predictive validity, which address neurodevelopmental aspects of the disorder, may bring us better understanding of the human disease and offer a novel strategy to explore unconventional treatment.