Document Detail

Cardiovascular responses to kappa opioid agonists in intact and adrenal demedullated rats.
MedLine Citation:
PMID:  2853675     Owner:  NLM     Status:  MEDLINE    
The effects of three kappa opioid agonists namely, bremazocine, tifluadom and U-50,488H were studied on blood pressure and heart rate in urethane-anesthetized normal and bilateral adrenal demedullated rats. Bremazocine (0.2, 0.4 and 0.6 mg/kg i.v.) produced a dose-dependent decrease in heart rate, while only 0.4 mg/kg bremazocine produced marked hypotension. The effect appeared to be long lasting because even at 60 min following drug administration the decreases in both heart rate and blood pressure continued. Bilateral adrenal demedullation did not change bremazocine-induced fall in blood pressure but the bradycardia was partially blocked. Tifluadom (0.1-0.4 mg/kg i.v.) produced an initial arrest of heart beat followed by bradycardia which recovered in about 60 min. Except for a very transient fall soon after drug administration no significant effect was observed on blood pressure. In adrenal demedullated rats, tifluadom induced initial arrest of heart was not affected but the subsequent bradycardia was blocked. U-50,488H (0.2, 0.4 and 0.6 mg/kg i.v.) produced dose-dependent bradycardia and hypotension both of which were blocked following bilateral adrenal demedullation. Naltrexone methylbromide (MRZ 2663 BR), a quaternary opioid antagonist, injected 5 min prior to U-50,488H, blocked its cardiovascular effects. The results suggest that kappa opioid agonists given i.v. depress cardiovascular system and these effects are mediated through the adrenal medulla and peripheral opioid receptors. The differential effects of kappa opioid agonists on blood pressure and heart rate suggest that either the three kappa agents interact differentially at the kappa opioid receptors or the subtypes of receptors for the kappa opioid exist.
A Gulati; H N Bhargava
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  European journal of pharmacology     Volume:  156     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1988 Nov 
Date Detail:
Created Date:  1989-05-15     Completed Date:  1989-05-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  247-57     Citation Subset:  IM    
Department of Pharmacodynamics, University of Illinois, Chicago 60612.
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MeSH Terms
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
Adrenal Medulla / physiology*,  surgery
Benzomorphans / pharmacology*
Blood Pressure / drug effects
Cardiovascular System / drug effects*
Dose-Response Relationship, Drug
Heart Rate / drug effects
Morphinans / pharmacology*
Naltrexone / pharmacology
Pyrrolidines / pharmacology*
Rats, Inbred Strains
Receptors, Opioid / antagonists & inhibitors*
Tape Recording
Grant Support
Reg. No./Substance:
0/Benzomorphans; 0/Morphinans; 0/Pyrrolidines; 0/Receptors, Opioid; 16590-41-3/Naltrexone; 67198-13-4/3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; 75684-07-0/bremazocine

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