Linked Life Data

18690108

Source:http://linkedlifedata.com/resource/pubmed/id/18690108

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
2008-8-11
pubmed:abstractText
Activity of the cholinergic muscarinic system is associated with modulation of locomotor activity, although the precise mechanism remains unclear. The phospholipase C-beta1 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-beta1 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0955-8810
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
543-7
pubmed:dateRevised
2009-7-7
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Role of muscarinic receptors in the activity of N-desmethylclozapine: reversal of hyperactivity in the phospholipase C knockout mouse.
pubmed:affiliation
Howard Florey Institute, University of Melbourne, Victoria, Australia. laura.gray@gms.edu.sg
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't