Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Risperidone (R 64 766, 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-pyperidinyl]ethyl )-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one) has superior effects in treating negative symptoms of schizophrenia and causes less extrapyramidal side effects than traditional antipsychotics. In this study, we employed the [14C]2-deoxy-D-glucose method to map local cerebral metabolic activity of rats acutely administrated i.p. with 0.0, 0.1, 0.5, 1.0 and 2.0 mg kg(-1) risperidone. Risperidone in the highest dose produced a reduction of glucose utilization in 11 of the 38 regions examined. The results showed that the regions with metabolic change are somewhat different from those results studied with microdialysis and the Fos immunohistochemistry. Among the nuclei with metabolic changes, the hippocampus and the mediodorsal nucleus of the thalamus may be related to the therapeutic action of risperidone and require further study.
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PMID:The effect of acute administration of risperidone on local cerebral glucose utilization in the rat. 1033

Serotonin-1A (5-HT(1A)) receptors have been implicated in the symptoms of schizophrenia. However, there is limited in vivo evidence for an interaction of antipsychotic drugs with 5-HT(1A) receptor-mediated behavioral effects. We therefore investigated in rats the action of several antipsychotic drugs on prepulse inhibition (PPI), a measure of sensorimotor gating that is deficient in schizophrenia. Disruption of PPI at the 100-ms interstimulus interval (ISI), but not the 30-ms ISI, was induced by treatment with 0.5 mg/kg 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), the 5-HT(1A) receptor agonist. In rats pretreated with 0.25 mg/kg haloperidol (4-[-4-(p-chlorophenyl)-4-hydroxypiperidino]-4'-fluoro butyrophenone) or raclopride [3,5-dichloro-N-(1-ethylpyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxybenzamide tartrate], the disruption of PPI was no longer significant. Of the atypical antipsychotic drugs clozapine (8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]-diazepine), olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine), risperidone [3-[2-[-4-(6-fluoro-1,2-benzisoxazol-3-yl) piperidino] ethyl-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one)], amisulpride (4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-o-anisamide), and aripiprazole (7-[4-[-4[-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydrocarbostyrilor 7-[4-[4-(2,3-dichlorophenyl) piperazin-1-yl]butoxy]-1,2,3,4,-tetrahydroquinolin-2-one), only aripiprazole significantly reduced the effect of 8-OH-DPAT on PPI. This effect was mimicked by pretreatment with the 5-HT(1A) receptor partial agonist, buspirone [N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione hydrochloride]. On the other hand, some of the antipsychotic drugs and other pretreatments showed complex, prepulse-dependent effects on their own. These data show little in vivo interaction of several atypical antipsychotic drugs with the disruption of PPI mediated by 5-HT(1A) receptor stimulation. The action of haloperidol and raclopride suggests a major involvement of dopamine D(2) receptors in this effect, possibly downstream from the initial serotonergic stimulation. The action of aripiprazole could be mediated by its partial agonist properties at 5-HT(1A) receptors or its dopamine D(2)-blocking properties.
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PMID:Differential effects of antipsychotic drugs on serotonin-1A receptor-mediated disruption of prepulse inhibition. 1719 99