Document Detail


Therapeutic potential of alpha2 adrenoceptor antagonism for antipsychotic-induced extrapyramidal motor disorders.
MedLine Citation:
PMID:  19429072     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined the effects of JP-1302 (a selective alpha2C antagonist), BRL-44408 (a selective alpha2A antagonist) and yohimbine (a non-selective alpha2 antagonist) on haloperidol-induced bradykinesia and catalepsy in mice to elucidate the role of alpha2 adrenoceptor subtypes in modifying extrapyramidal motor disorders. JP-1302 (0.1-1 mg/kg, s.c.) dose-dependently ameliorated haloperidol-induced bradykinesia in the pole-test and reversed the catalepsy time increased by haloperidol. Antibradykinetic and anticataleptic actions of JP-1302 were statistically significant at 0.3 and 1 mg/kg, and these doses did not alter the ambulatory distance, rearing or center-perimeter residence time in the open-field test. BRL-44408 (1-10 mg/kg, s.c.) and yohimbine (0.3-3 mg/kg, i.p.) also ameliorated haloperidol-induced bradykinesia and catalepsy. However, both agents significantly decreased ambulatory distance and rearing in the open-field test, possibly reflecting their anxiogenic actions associated with alpha2A antagonism. The present study shows for the first time that blockade of alpha2C receptors can alleviate antipsychotic-induced extrapyramidal motor disorders without affecting gross behaviors.
Authors:
Junta Imaki; Yukari Mae; Saki Shimizu; Yukihiro Ohno
Publication Detail:
Type:  Journal Article     Date:  2009-03-05
Journal Detail:
Title:  Neuroscience letters     Volume:  454     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-08-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  143-7     Citation Subset:  IM    
Affiliation:
Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acridines / therapeutic use
Adrenergic alpha-Antagonists / therapeutic use
Analysis of Variance
Animals
Antipsychotic Agents / toxicity
Catalepsy / chemically induced,  drug therapy*
Dose-Response Relationship, Drug
Haloperidol / toxicity*
Hypokinesia / chemically induced,  drug therapy*
Imidazoles / therapeutic use
Isoindoles / therapeutic use
Male
Mice
Motor Activity / drug effects
Piperazines / therapeutic use
Receptors, Adrenergic, alpha-2 / antagonists & inhibitors*
Yohimbine / therapeutic use
Chemical
Reg. No./Substance:
0/Acridines; 0/Adrenergic alpha-Antagonists; 0/Antipsychotic Agents; 0/Imidazoles; 0/Isoindoles; 0/JP-1302; 0/Piperazines; 0/Receptors, Adrenergic, alpha-2; 118343-19-4/BRL 44408; 146-48-5/Yohimbine; 52-86-8/Haloperidol

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


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