Affiliation:
1. University of Kalmar, Department of Natural Sciences, Norra Vagen 49, SE-391 82 Kalmar, Sweden.
Abstract
Most second-generation, atypical, dopamine (DA) D2/5-HT2 blocking antipsychotics still induce extrapyramidal side effects (EPS) in higher doses. Weight gain and metabolic disturbances are also a problem, and negative and cognitive symptoms have not been sufficiently addressed. The current brain DA mesolimbic hyperactive/mesocortical hypoactive hypothesis of schizophrenia suggests that DA D2/5-HT1A receptor partial agonist properties may be more efficacious with less side effects. DA D2 receptor partial agonists may stabilize a hyperactive/hypoactive DA condition. Additional 5-HT1A stimulation may enhance therapeutic efficacy and also improve EPS liability profile. In clinical trials in schizophrenic patients, the novel DA D2/5-HT1A partial agonist bifeprunox indeed demonstrates therapeutic efficacy, a safe EPS profile and appears beneficial regarding weight gain, prolactin, blood lipid and glucose levels and cardiac rhythm. The data on bifeprunox are promising and suggest that combined DA D2/5-HT1A partial agonism may well be important properties for future-generation antipsychotics.
Subject
Clinical Neurology,Neurology
Cited by
20 articles.
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