Document Detail


Effects of JL13, a pyridobenzoxazepine with potential atypical antipsychotic activity, in animal models for schizophrenia.
MedLine Citation:
PMID:  11408566     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
JL13 [5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5] benzoxazepine fumarate] is a substance with a close structural resemblance to clozapine. However, it is less sensitive to oxidation and may therefore have less hematological side effects. In the present study, JL13 was compared with clozapine and haloperidol in several animal models for schizophrenia. The paw test represents a screening model for antipsychotic drugs that can discriminate between drugs with extrapyramidal side effects and drugs without. Haloperidol increased both forelimb retraction time and hindlimb retraction time (HRT), whereas both clozapine and JL13 increased only HRT. In the prepulse inhibition paradigm, all three drugs reversed the apomorphine- and the amphetamine-induced disruption of prepulse inhibition. However, whereas haloperidol was equally effective against both dopaminergic drugs, JL13 and clozapine were more effective against amphetamine. Finally, only JL13 was able to increase prepulse inhibition in normal rats, whereas only clozapine reduced basal startle amplitude. Taken together, these data suggest that JL13 may be an effective antipsychotic drug, with a profile similar to clozapine.
Authors:
B A Ellenbroek; J F Liégeois; J Bruhwyler; A R Cools
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  298     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-06-15     Completed Date:  2001-07-19     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  386-91     Citation Subset:  IM    
Affiliation:
Department of Psychoneuropharmacology, University of Nijmegen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Amphetamine
Animals
Antipsychotic Agents / pharmacology*,  therapeutic use
Benzodiazepinones / chemistry
Central Nervous System Stimulants
Clozapine / analogs & derivatives,  pharmacology*,  therapeutic use
Disease Models, Animal*
Drug Evaluation, Preclinical
Haloperidol / pharmacology,  therapeutic use
Locomotion / drug effects*,  physiology
Male
Pyridines / chemistry
Rats
Rats, Wistar
Schizophrenia* / drug therapy
Startle Reaction / drug effects*,  physiology
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 0/Benzodiazepinones; 0/Central Nervous System Stimulants; 0/Pyridines; 10321-12-7/propizepine; 174762-89-1/JL 13 compound; 300-62-9/Amphetamine; 52-86-8/Haloperidol; 5786-21-0/Clozapine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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