Document Detail


Nasal administration of the calcium channel blocker diltiazem decreases food intake and attenuates weight gain in rats.
MedLine Citation:
PMID:  16214208     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Food intake is normally influenced by a multitude of complex endogenous neurochemical systems, in addition to numerous external environmental stimuli, including olfaction. Since most olfactory neurons process odorant exposures through Ca2+-mediated mechanisms via Ca2+ channels, a novel approach at influencing the ingestive behaviors of animals might therefore involve altering olfactory acuity via Ca2+ channel blockade. We tested the ability of a Ca2+ channel blocker, diltiazem, to alter food intake in hyperphagic rats when administered using the intranasal (i.n.), intraperitoneal (i.p.), oral (p.o.) or intracerebroventricular (i.c.v.) routes of administration. Male Sprague Dawley rats, which had been food-deprived for 4 h at the beginning of the dark cycle, were administered different doses of diltiazem (0-8 mg/animal or 0-40 mg/kg) and the amounts of food consumed were measured. While food intake at 1, 2 and 4 h post drug administration was significantly decreased in a dose-dependent manner after i.n. administration, the i.p., p.o., and i.c.v. routes did not affect food intake. In another experiment, rats trained to eat their daily meal during the first 4 h at the onset of the dark cycle and treated daily with i.n. diltiazem (0-8 mg/animal) prior to food introduction exhibited a significantly decreased rate of weight gain in a dose-dependent manner over a 14-day period. Both i.n. and i.p. diltiazem significantly increased the plasma drug concentration at 1 h, however there was no significant difference between these routes of administration. Additional studies failed to demonstrate any detrimental effects of i.n. diltiazem (0-8 mg/animal) on conditioned taste aversion, locomotion or gross neurological/behavioral competence using the rota-rod test. While a local action on the nasal odorant receptors is most likely the site of diltiazem's action, further studies are needed to determine the exact mechanism of action of i.n. diltiazem.
Authors:
Ahmed Amer; Timothy J Maher
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Publication Detail:
Type:  Journal Article     Date:  2005-10-07
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  82     ISSN:  0091-3057     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-11-29     Completed Date:  2006-03-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  379-87     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences, 179 Longwood Avenue, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Administration, Intranasal
Animals
Avoidance Learning / drug effects
Calcium Channel Blockers / administration & dosage,  pharmacology*
Depression, Chemical
Diet
Diltiazem / administration & dosage,  pharmacology*
Dose-Response Relationship, Drug
Eating / drug effects*
Food Deprivation / physiology
Injections, Intraperitoneal
Injections, Intraventricular
Male
Psychomotor Performance / drug effects
Rats
Rats, Sprague-Dawley
Taste / drug effects
Weight Gain / drug effects*
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 42399-41-7/Diltiazem

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


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