Linked Life Data

12586203

Source:http://linkedlifedata.com/resource/pubmed/id/12586203

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2003-2-14
pubmed:abstractText
An atypical antipsychotic drug, zotepine, which is pharmacologically and clinically related to clozapine, has unique therapeutic effects on patients with schizophrenia. It has been demonstrated that clozapine blocks neurotoxicity in the rat retrosplenial cortex induced by administration of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine ((+)-MK-801). We examined whether or not zotepine has the ability to block neurotoxicity in the rat retrosplenial cortex induced by administration of dizocilpine. Female Sprague-Dawley rats were injected intraperitoneally (i.p.) with vehicle (1 mg/kg), zotepine (5, 10 or 20 mg/kg) or clozapine (20 mg/kg). Fifteen minutes later, animals were injected intraperitoneally (i.p.) with vehicle (1 ml/kg) or dizocilpine (0.5 mg/kg). Neuropathological changes (neuronal vacuolization) were assessed 4 h after administration of dizocilpine. Immunohistochemical analysis of heat shock protein HSP-70, a marker of reversible neuronal injury, was performed 24 h after administration of dizocilpine. The pretreatment with zotepine (5, 10 or 20 mg/kg) significantly decreased the number of vacuolized neurons in the rat retrosplenial cortex 4 h after the administration of dizocilpine (0.5 mg/kg), in a dose-dependent manner. The potency of zotepine (20 mg/kg) for dizocilpine-induced neurotoxicity was similar to that of clozapine (20 mg/kg). Furthermore, similar to the case with clozapine (20 mg/kg, i.p.), zotepine (20 mg/kg, i.p.) significantly attenuated the expression of HSP-70 in the rat retrosplenial cortex induced by dizocilpine (0.5 mg/kg, i.p.). The present study suggests that the neuroprotective effects of zotepine- on dizocilpine-induced neurotoxicity are equipotent to those of clozapine. Based on the NMDA receptor hypofunction hypothesis of schizophrenia, the efficacy of zotepine in this study may partly contribute to the unique therapeutic effects of zotepine in patients with schizophrenia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-2999
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Elsevier Science B.V.
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
461
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-8
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Protective effect of the antipsychotic drug zotepine on dizocilpine-induced neuropathological changes in rat retrosplenial cortex.
pubmed:affiliation
Department of Psychiatry (K2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoku, Chiba, Chiba 260-8670, Japan. okmnaoe@hotmail.com
pubmed:publicationType
Journal Article