This paper is only available as a PDF. To read, Please Download here.
Objective: Our purpose was to assess the effects of an intravenous dose of a highly selective
μ-(DALDA) and δ-(DPDPE) opioid peptide to determine which class of peptide has the
best clinical potential.
Study design: Chronically instrumented pregnant ewes recieved 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.
Conclusion: The δ-selective agonist had multiple nonopioid adverse effects, whereas the μ-selective
agonist was well tolerated by the pregnant ewe, suggesting that μ-selective agonists
have better potential for clinical use as an analgesic in pregnancy.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of Obstetrics & GynecologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Pharmacology of opioids.Pharmacol Rev. 1984; 35: 285-323
- A brief history of opiates, opioid peptides and opioid receptors.in: Proc Natl Acad Sci. 90. 1993: 5391-5393
- Maternal cardiovascular and metabolic responses to intravenous Tyr-D-Ala-Gly-Phe(N-Me)-Gly-ol (DAMGO) in chronically instrumented pregnant sheep.Analgesia. 1996; 2: 137-143
- Opposite effects of δ and μ-opioid receptor agonists on ventilation in conscious adult dogs.Brain Res. 1984; 323: 73-78
- Sympathoadrenal, cardiovascular and blood gas responses to highly selective mu and delta opioid peptides.J Pharmacol Exp Ther. 1989; 251: 1096-1103
- Comparison of cardiovascular effects of μ- and δ-opioid receptor agonists in dogs with congestive heart failure.Am J Physiol. 1994; 267: H912-H917
- Renal effects of TAPP, a highly selective μ-opioid agonist.Br J Pharmacol. 1996; 119: 239-244
- Stress-induced activation of sympathetic nervous system is attenuated by the δ-opioid receptor agonist deltorphin in healthy man.J Clin Endocrinol Metab. 1993; 77: 1490-1494
- Hytten F Chamberlain G Clinical physiology in obstetrics. Blackwell Scientific, London1991
- Maternal physiological adaptations to early human pregnancy.Am J Obstet Gynecol. 1988; 159: 1456-1460
- Blood-brain barrier transport of neuropeptides: analysis with a metabolically stable dermorphin analogue.Am J Physiol. 1994; 267: E124-E131
- Opioid depression of respiration in neonatal rats.J Physiol. 1995; 485: 3
- Opioid depression of respiration in neonatal rats.J Physiol. 1995; 485: 845-855
- TIPP[ψ]: a highly potent and stable pseudopeptide δ opioid receptor antagonist with extraordinary δ selectivity.J Med Chem. 1993; 36: 3182-3187
- Statistical principles in experimental design.McGraw-Hill, Baltimore1971
- Cardiovascular and respiratory effects of mu-, delta- and kappa-opiate agonists in-jected into the anterior hypothalamic brain area of awake rats.J Pharmacol Exp Ther. 1983; 225: 735-741
- Differential cardiovascular and respiratory responses to central administration of selective opioid agonists in conscious rabbits: correlation with receptor distribution.J Pharmacol. 1989; 98: 903-913
- Hypothalamic opioid μ-receptors regulate discrete hemodynamic functions in the conscious rat.Neuropharmacol. 1991; 30: 143-152
- Inhibition via opioid μ- and δ-receptors of vagal transmission in the rabbit.Arch Pharmacol. 1984; 328: 186-190
Article Info
Publication History
Accepted:
August 4,
1997
Received in revised form:
July 23,
1997
Received:
March 11,
1997
Footnotes
1Supported in part by NIDA grant DA08924.
Identification
Copyright
© 1998 Mosby, Inc. Published by Elsevier Inc.
