Please use this identifier to cite or link to this item: https://doi.org/10.1097/FBP.0b013e32830c3669
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dc.titleRole of muscarinic receptors in the activity of N-desmethylclozapine: Reversal of hyperactivity in the phospholipase C knockout mouse
dc.contributor.authorGray, L.
dc.contributor.authorMcOmish, C.
dc.contributor.authorScarr, E.
dc.contributor.authorDean, B.
dc.contributor.authorHannan, A.J.
dc.date.accessioned2016-11-11T07:59:58Z
dc.date.available2016-11-11T07:59:58Z
dc.date.issued2008-09
dc.identifier.citationGray, L., McOmish, C., Scarr, E., Dean, B., Hannan, A.J. (2008-09). Role of muscarinic receptors in the activity of N-desmethylclozapine: Reversal of hyperactivity in the phospholipase C knockout mouse. Behavioural Pharmacology 19 (5-6) : 543-547. ScholarBank@NUS Repository. https://doi.org/10.1097/FBP.0b013e32830c3669
dc.identifier.issn09558810
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/130015
dc.description.abstractActivity of the cholinergic muscarinic system is associated with modulation of locomotor activity, although the precise mechanism remains unclear. The phospholipase C-β1 knockout mouse displays both M1 muscarinic receptor dysfunction and a hyperactive locomotor phenotype. This mouse serves as an ideal model for the analysis of muscarinic modulation of locomotor activity. The clozapine metabolite N-desmethylclozapine (NDMC) has shown some promise as an alternative or adjunct treatment for psychotic disorders. NDMC shows strong muscarinic acetylcholine receptor affinities, which may contribute to the clinical efficacy of clozapine and account for the correlation between NDMC/clozapine ratio and treatment response. Administration of NMDC reversed a striking hyperactive phenotype in the phospholipase C-β1 knockout mouse, whereas no significant effects were observed in wild-type animals. This highlights the potential role of muscarinic activity in the behavioural response to NDMC. The M1 muscarinic antagonist pirenzepine, however, also reduced the hyperactive phenotype of these mice, emphasizing the importance of muscarinic function in the control of locomotor behaviour, but also calling into question the specific mechanism of action of NMDC at muscarinic receptors. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1097/FBP.0b013e32830c3669
dc.sourceScopus
dc.subjectLocomotor activity
dc.subjectMouse
dc.subjectMuscarinic receptors
dc.subjectN des-methylclozapine
dc.subjectPhospholipase C-β1 knockout
dc.typeArticle
dc.contributor.departmentDUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE
dc.description.doi10.1097/FBP.0b013e32830c3669
dc.description.sourcetitleBehavioural Pharmacology
dc.description.volume19
dc.description.issue5-6
dc.description.page543-547
dc.description.codenBPHAE
dc.identifier.isiut000258763900012
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