PET Studies in the Early Clinical Development of a New Antipsychotic

Abstract

The aetiology of psychotic illnesses, in particular schizophrenia, remains elusive; many theories have been put forward but to date there is no all encompassing and satisfactory hypothesis [1]. The therapeutic effects of antipsychotic drugs are generally considered to be associated with blockade of dopamine receptors, especially dopamine D₂ receptors [2,3]. In spite of their undeniable clinical usefulness treatment of psychotic patients with these antipsychotic drugs is often accompanied by unwanted side-effects. Acute extrapyramidal syndromes (EPS) are most prominent and may during long-term treatment be followed by irreversible tardive dyskinesia. In addition, some patients do not respond to treatment with the antipsychotic drugs that are available today. For these and other reasons the search for better antipsychotic drugs with improved clinical efficacy and/or less disturbing side-effects continues. Increasingly attention is being focused on other dopamine receptor subtypes than the dopamine D₂ receptor, e.g., D₁ D₃, and D₄ receptors, but also serotonin receptor subtypes, sigma receptors, and glutamate receptors [4]. One of the hypotheses concerning the pathophysiology of schizophrenia is the involvement of both dopamine and serotonin neurotransmitter systems [5].