Cardiovascular and metabolic responses to two receptor-selective opioid agonists in pregnant sheep.
OBJECTIVE
Our purpose was to assess the effects of an intravenous dose of a highly selective mu-(DALDA) and delta-(DPDPE) opioid peptide to determine which class of peptide has the best clinical potential.


METHODS
Chronically instrumented pregnant ewes received a 0.3 mg/kg intravenous bolus of each peptide with and without opioid receptor blockade by means of a randomized prospective design.


RESULTS
Intravenous DALDA produced only mild hypertension and a loss of heart rate variability, whereas DPDPE produced respiratory depression, maternal hypertension, and a fall in heart rate in both mother and fetus. Uterine blood flow, oxygen uptake, and glucose uptake were unchanged with both drugs. The effects of DALDA but not DPDPE were reversed by opioid receptor blockade.


CONCLUSIONS
The delta-selective agonist had multiple nonopioid adverse effects, whereas the mu-selective agonist was well tolerated by the pregnant ewe, suggesting that mu-selective agonists have better potential for clinical use as an analgesic in pregnancy.
Clapp
J F
JF
Department of Reproductive Biology and Obstetrics and Gynecology, Case Western University and MetroHealth Medical Center, Cleveland, Ohio 44106, USA.
Kett
A
A
Olariu
N
N
Omoniyi
A T
AT
Wu
D
D
Kim
H
H
Szeto
H H
HH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012119:Respiration / Q000187:drug effects; D012756:Sheep; D014599:Uterus / Q000098:blood supply
D001786:Blood Glucose; D004745:Enkephalins; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C063076:tyrosyl-arginyl-phenylalanyl-lysinamide; D020881:Enkephalin, D-Penicillamine (2,5)-