Linked Life Data

11999907

Source:http://linkedlifedata.com/resource/pubmed/id/11999907

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-5-9
pubmed:abstractText
Iloperidone is a novel atypical antipsychotic compound currently under clinical development for the treatment of psychotic disorders. In radioligand binding studies, iloperidone binds with high affinity to serotonin (5-HT) 5-HT2A and noradrenaline alpha1 and alpha2C receptors [Neuropsychopharmacology (2001) 25, 904-914]. The human metabolism of iloperidone generates two major metabolites, P88-8991 and P95-12113. The aim of this study was to compare the receptor affinity profile of P88-8991 and P95-12113 with that of the parent compound. The receptor affinity profile of P88-8991 is comparable to that of iloperidone. This metabolite binds to the following monoamine receptors (pKi values in nM): serotonin 5-HT2A receptors (9.56), adrenergic alpha1 (8.08) and alpha2C (7.79) receptors, and D2A receptors (7.80). Lower affinity is seen for other dopamine, serotonin, alpha2-adrenergic and histamine H1 receptors. In contrast, P95-12113 shows affinity for 5-HT2A receptors (pKi 8.15; which is 60-fold lower than that of iloperidone), adrenergic alpha1 (7.67), alpha2C (7.32) and alpha2B (7.08) receptors. Given this affinity profile, and the observation that P95-12113 does not readily cross the blood-brain barrier, it is unlikely that this metabolite contributes to the therapeutic effect of iloperidone in patients with schizophrenia. However, the comparable receptor binding profile of P88-8991 indicates that it is likely to contribute to the clinical profile of iloperidone.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0278-5846
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
553-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Receptor profile of P88-8991 and P95-12113, metabolites of the novel antipsychotic iloperidone.
pubmed:affiliation
Novartis Pharma AG, Research Nervous System, Basel, Switzerland.
pubmed:publicationType
Journal Article, Comparative Study