Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychosis, linked to chronic levodopa and other antiparkinsonian drug treatments, is a common and incapacitating complication of advanced Parkinson's disease (PD). The psychosis may be due, in part, to overstimulation of central serotonergic (5-HT) receptors. We treated 16 PD patients who had psychosis of 6 to 60 months' duration with the 5-HT3 receptor antagonist ondansetron (12 to 24 mg daily) in an open-label, short-term (4 to 8 weeks) trial. There was marked to moderate improvement (p < 0.01) in measures of visual hallucinations, paranoid delusions, confusion, and the associated global functional impairment in all but one of the patients, and there was moderate improvement in the Brief Psychiatric Rating Scale and the Nurse's Observation Scale for Inpatient Evaluation; the Mini-Mental State Examination scores remained unaltered. Ondansetron did not cause any worsening in basic PD symptoms or levodopa efficacy and was well tolerated with no major side effects. Our study suggests that pharmacologic blockade of central 5-HT receptors may become a strategy to attenuate PD psychosis without inducing motor deterioration or suppression of antiparkinsonian action of levodopa, and it lends support to the hypothesis that serotonergic mechanisms are pathogenetically important in the emergence of psychosis in PD.
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PMID:Psychosis in advanced Parkinson's disease: treatment with ondansetron, a 5-HT3 receptor antagonist. 896 Jul 64

Cognitive deficits in schizophrenia are the core symptoms of this disorder, and are strongly correlated with decreased QOL in patients. Antipsychotic drugs have been used therapeutically for positive symptoms, including hallucinations and delusions. However, many patients treated with antipsychotic drugs fail to recover from cognitive deficits. Therefore, a number of new therapeutic drugs for cognitive deficits in schizophrenia are currently being developed around the world. A number of studies suggest that nicotine, a major component of cigarettes, could improve cognitive deficits in patients with schizophrenia. Accumulating evidence suggests that the alpha7 subtype of nicotinic receptors (alpha7 nAchRs) play a role in the pathophysiology of schizophrenia, as well as deficits in auditory evoked potential P50 in patients with schizophrenia. We have reported that the antiemetic drug tropisetron (alpha7 nAchR agonist and 5-HT3 receptor antagonist) improved auditory P20-N40 deficits in DBA/2 mice, and cognitive deficits after administration of the NMDA receptor antagonist phencyclidine. Furthermore, a single administration of tropisetron was associated with improved auditory P50 deficits in non-smoking patients with schizophrenia. Moreover, a randomized, double-blind, placebo-controlled study demonstrated that tropisetron significantly improved auditory P50 deficits and attention deficits in patients with schizophrenia. In this paper, the author will discuss the therapeutic potential of alpha7 nAChR agonists for cognitive deficits in patients with schizophrenia.
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PMID:[Development of new therapeutic drugs based on the pathophysiology of schizophrenia]. 2170 28