Document Detail

Effects of flunarizine and diltiazem on physical dependence on barbital in rats.
MedLine Citation:
PMID:  8392734     Owner:  NLM     Status:  MEDLINE    
The effects of flunarizine and diltiazem both on development of physical dependence on barbital and on barbital withdrawal signs in rats were examined using the drug-admixed food (DAF) method. Rats were chronically treated with barbital or barbital in combination with flunarizine (fixed at 1.5 mg/g of food) or diltiazem (fixed at 0.75 mg/g of food)-admixed food on the schedule of gradually increasing doses of barbital. Motor incoordination during the treatment was potentiated by coadministration of flunarizine, but not by coadministration of diltiazem. After the termination of drug treatment, the body weight loss and withdrawal scores were significantly suppressed in the group coadministered flunarizine, but not in that coadministered diltiazem. There were no significant differences in plasma barbital levels after the withdrawal between groups. In the substitution test, flunarizine (20 and 40 mg/kg, IP) significantly suppressed the body weight loss and withdrawal scores after the withdrawal, but diltiazem (20 mg/kg, IP) did not. These results indicated that flunarizine suppressed both the development of physical dependence on barbital and barbital withdrawal signs, mainly according to the suppression of convulsions, but not diltiazem, which is known to poorly penetrate into the brain. Therefore, the present findings suggest that central calcium channels may be involved in both the development of physical dependence on barbital and the appearance of barbital withdrawal signs.
T Suzuki; H Mizoguchi; H Noguchi; T Yoshii; M Misawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  45     ISSN:  0091-3057     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-08-19     Completed Date:  1993-08-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  703-12     Citation Subset:  IM    
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
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MeSH Terms
Barbital / blood,  pharmacokinetics,  pharmacology*
Calcium Channel Blockers / pharmacology*
Calcium Channels / drug effects
Diltiazem / pharmacology*
Flunarizine / pharmacology*
Postural Balance / drug effects
Rats, Sprague-Dawley
Substance Withdrawal Syndrome / psychology
Substance-Related Disorders / psychology*
Weight Loss / drug effects
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Calcium Channels; 42399-41-7/Diltiazem; 52468-60-7/Flunarizine; 57-44-3/Barbital

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

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