Document Detail


Effects of tryptophan and valine administration on behavioral pharmacology of haloperidol.
MedLine Citation:
PMID:  16431394     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Development of antipsychotics with slight/no extra-pyramidal symptoms (EPS) and/or other side effects is one of the exploring fields of drug research. Haloperidol is a high potency typical neuroleptic used in the treatment of schizophrenia but produces muscles related side effects commonly known as EPS. These effects are not produced following the administration of atypical neuroleptics such as clozapine. A severe side effect of clozapine treatment is however, agranulocytosis. This involves investigation on the mechanism by which a typical neuroleptic acting via serotonergic mechanism tends to produce less or no EPS. The present study was, therefore, designed to determine the effect of serotonin precursor tryptophan and a large neutral amino acid other than tryptophan (valine) on the modulation of haloperidol induced catalepsy and akinesia. Cataleptic effects of the drug and activity reducing effects were monitored on inclined surface and in an activity box or open field respectively. The results are discussed in the context of a role of tryptophan and valine induced changes of brain serotonin in modifying the extrapyramidal and monoaminergic effects of the typical neuroleptic haloperidol. In the present study administration of TRP and valine decreased activity in rats, haloperidol-induced catalepsy' was not modulated by prior administration of tryptophan or valine. Brain serotonin levels were elevated by haloperidol treatment and correlated very well with the behavioral response. These findings suggest a possible serotonergic involvement in neuroleptic induced tardive dyskinesia and an amelioration of the disorder through TRP supplementation.
Authors:
Obaid Ali; Darakhshan J Haleem; Zafar Saied Saify; Noor Kamil; Roohi Obaid; Syed Waseemuddin Ahmed
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Pakistan journal of pharmaceutical sciences     Volume:  18     ISSN:  1011-601X     ISO Abbreviation:  Pak J Pharm Sci     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2006-01-24     Completed Date:  2006-03-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9426356     Medline TA:  Pak J Pharm Sci     Country:  Pakistan    
Other Details:
Languages:  eng     Pagination:  23-8     Citation Subset:  IM    
Affiliation:
Central Drugs Laboratory, Ministry of Health, Government of Pakistan, Pakistan. mobaidali@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antipsychotic Agents / administration & dosage,  pharmacology,  toxicity
Behavior, Animal / drug effects*
Catalepsy / chemically induced,  prevention & control
Drug Administration Schedule
Drug Interactions
Haloperidol / administration & dosage,  pharmacology*,  toxicity
Injections, Intraperitoneal
Male
Motor Activity / drug effects
Rats
Rats, Wistar
Tryptophan / administration & dosage,  pharmacology*
Valine / administration & dosage,  pharmacology*
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 52-86-8/Haloperidol; 7004-03-7/Valine; 73-22-3/Tryptophan

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


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