Document Detail

Cardiovascular and respiratory actions of U50,488H in the unanaesthetized ovine foetus.
MedLine Citation:
PMID:  8851169     Owner:  NLM     Status:  MEDLINE    
In an effort to evaluate the feasibility of kappa-opioid receptor agonists for use in pregnancy, we have investigated the actions of U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)cyclohexyl]benzeneacetamide) on cardiovascular and respiratory control in the unanaesthetized ovine foetus. Intravenous administration of U50,488H (1.0 mg/kg) to the foetus resulted in an immediate increase in foetal blood pressure (P < 0.0001) and heart rate (P < 0.0001) which lasted 15 min, followed by a prolonged loss of heart rate variability for up to 3 h. There was also a significant suppression of foetal breathing movements for 2-3 h (P < 0.008). Pretreatment with naloxone (12 mg/h) completely blocked the hypertensive and tachycardiac response to U50,488H, but was unable to prevent the loss of variation in heart rate or respiratory depression. These data suggest that U50,488H can exert direct cardiovascular and respiratory actions in the ovine foetus via both opioid and non-opioid mechanisms. The naloxone-insensitive suppression of foetal breathing would severely limit the use of U50,488H as an obstetrical analgesic.
H H Szeto; D Wu; P Y Cheng; Y Soong; C C Taylor; J Yee
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  European journal of pharmacology     Volume:  297     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-12-05     Completed Date:  1996-12-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  77-82     Citation Subset:  IM    
Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA.
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MeSH Terms
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
Antihypertensive Agents / pharmacology*
Blood Gas Analysis
Blood Pressure / drug effects
Fetus / physiology*
Heart Rate, Fetal / drug effects
Hemodynamics / drug effects*
Naloxone / antagonists & inhibitors,  pharmacology
Narcotic Antagonists / pharmacology
Pyrrolidines / pharmacology*
Respiratory Mechanics / drug effects*
Grant Support
02475-16//PHS HHS; 08924-01//PHS HHS; DA07274-04/DA/NIDA NIH HHS
Reg. No./Substance:
0/Antihypertensive Agents; 0/Narcotic Antagonists; 0/Pyrrolidines; 465-65-6/Naloxone; 67198-13-4/3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer

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