sr-142801 and Schizophrenia

Although current antipsychotic drugs are effective at treating the psychotic (positive) symptoms of schizophrenia, they have one or more serious side effects, including extrapyramidal symptoms, weight gain, cardiovascular liabilities and type II diabetes. However, recent data from clinical trials of selective neurokinin 3 (NK(3)) receptor antagonists in schizophrenia - osanetant and talnetant - have shown significant improvement in positive symptoms, with no major side-effects reported as yet. Here we discuss the preclinical and clinical evidence that indicates that NK(3) receptor antagonists might represent a new approach to the treatment of schizophrenia and possibly other neuropsychiatric disorders.

Topics: Animals; Antipsychotic Agents; Humans; Piperidines; Receptors, Neurokinin-3; Schizophrenia

Osanetant is a neurokinin (NK3) receptor antagonist under development by Sanofi-Synthélabo (formerly Sanofi) as a potential treatment for schizophrenia [328910]. Sanofi was originally investigating its potential use as a treatment for psychosis and anxiety [169511]. Following phase IIa clinical trials [307656], [328910], [359231], osanetant entered phase IIb development in February 2001 [409432]. Osanetant was the first potent and selective non-peptide antagonist described for the NK3 tachykinin receptor [176305]. It has a higher affinity for human and guinea pig NK3 receptors than for rat NK3 receptors [176305]. In October 1999, Lehman Brothers predicted that the probability of the product reaching the market was 10%, with a possible launch in 2003 and potential peak sales of US $200 million in 2011 [346267].

Topics: Acetylcholine; Animals; Antipsychotic Agents; Brain; Cardiovascular System; Dopamine; Humans; Piperidines; Receptors, Neurokinin-3; Schizophrenia; Stereoisomerism; Structure-Activity Relationship; Tachykinins

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Data Interpretation, Statistical; Humans; Mianserin; Mirtazapine; Neurotensin; Peptide Fragments; Piperidines; Pyrazoles; Quinolines; Receptors, Neurotensin; Research Design; Schizophrenia; Schizophrenic Psychology; Treatment Outcome