| Cardiovascular responses to melanocortin 4-receptor stimulation in conscious unrestrained normotensive rats. | |
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MedLine Citation:
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PMID: 16274849 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the present studies, we used a non-selective melanocortin MC3/4 receptor agonist (HP228) and a novel selective melanocortin MC4 receptor (MC4-R) agonist (MK-cpd1) to study the cardiovascular, temperature, locomotor and feeding responses to melanocortin receptor stimulation in comparison to sibutramine in rats instrumented with a telemetry transmitter. Moreover, norepinephrine turnover rates in heart and brown adipose tissue were determined. HP228 (1, 3 and 10mg/kg, i.p.) reduced 24h food intake dose-dependently and increased heart rate and mean arterial pressure (maximal differences: +60+/-8beats/min and +8+/-1mmHg, means+/-S.E.M., p<0.001 and p<0.01, respectively). After 10mg/kg HP228 showed a three-fold increase in norepinephrine turnover in the heart. The selective MC4-R agonist MK-cpd1 tended to decrease 24h food intake only at the highest dose tested (10mg/kg, i.p., p=0.06) and increased both heart rate (+17+/-4 and +22+/-5beats/min at 3 and 10mg/kg, p<0.01) and mean arterial pressure (+4+/-1mmHg at 10mg/kg, p<0.05). Sibutramine reduced food intake at all doses tested (1, 3 and 10mg/kg, i.p.). It did not change mean arterial pressure significantly, and increased heart rate only at the highest dose tested (+36+/-6beats/min, p<0.05). If also observed in humans, the pharmacological profile of MC4-R agonists would not offer a significant therapeutic advantage over currently used appetite suppressants such as sibutramine. |
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Authors:
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Ulrich Nordheim; Janet R Nicholson; Karol Dokladny; Patrick Dunant; Karl G Hofbauer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-11-07 |
Journal Detail:
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Title: Peptides Volume: 27 ISSN: 0196-9781 ISO Abbreviation: Peptides Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-01-31 Completed Date: 2006-05-25 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8008690 Medline TA: Peptides Country: United States |
Other Details:
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Languages: eng Pagination: 438-43 Citation Subset: IM |
Affiliation:
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Chair for Applied Pharmacology, Biozentrum/Pharmazentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Body Temperature Cardiovascular Physiological Phenomena / drug effects* Cyclobutanes / administration & dosage, pharmacology* Feeding Behavior / drug effects Male Oligopeptides / administration & dosage, pharmacology* Rats Rats, Sprague-Dawley Receptor, Melanocortin, Type 4 / drug effects, metabolism* Tetrahydroisoquinolines / pharmacology Triazoles / pharmacology Wakefulness / physiology |
| Chemical | |
Reg. No./Substance:
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0/Cyclobutanes; 0/N-(1,2,3,4-tetrahydroisoquinolinium-3-ylcarbonyl)-1-(4-chlorobenzyl)-2-(4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl)-2-oxoethylamine; 0/Oligopeptides; 0/Receptor, Melanocortin, Type 4; 0/Tetrahydroisoquinolines; 0/Triazoles; 106650-56-0/sibutramine; 109022-88-0/HP 228 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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