Morphine-3-glucuronide has a minor effect on morphine antinociception. Pharmacodynamic modeling

Journal of Pharmaceutical Sciences
M GårdmarkM Hammarlund-Udenaes

Abstract

The objective of this study was to quantify the influence of morphine-3-glucuronide (M3G) on the morphine antinociceptive effect (ANE) and respiratory effects in the rat. Three groups of rats were pretreated with either saline or M3G at two different rates. Morphine infusion of 10 mg/h/kg (group A) or 20 mg/h/kg (group B) was administered to each pretreatment group for 3 h. The ANE was measured by the electrical stimulation vocalization method, and blood gas parameters (pCO2, pO2, and pH) were assessed. Independent of pretreatment all groups displayed a concurrent increase in the ANE. The maximal effect diverged between pretreatments. Acute tolerance was observed, but no rebound effect was detected. To characterize the ANE, an effect compartment model and an indirect response model were selected, both capable of describing the observed features. In both models incorporation of M3G led to a better explanation of the data. On the basis of the parameters obtained in the fits, naturally occurring M3G would reduce the antinociceptive effect during a morphine infusion (plasma concentration 15 microM) by 15-20%. The exposure of M3G did not significantly change the respiratory response following the morphine treatment.

References

Apr 1, 1991·Journal of Pharmacobio-dynamics·C K KuoH Yoshimura
Sep 1, 1990·Clinical Pharmacology and Therapeutics·H J McQuayR A Moore
Jan 1, 1990·Life Sciences·M T SmithT Cramond
Dec 28, 1987·Life Sciences·G W PasternakC E Inturrisi
Jul 27, 1985·Lancet·J SäweI Odar-Cederlöf
Jan 1, 1987·Pharmacology & Toxicology·C B Christensen, L N Jørgensen
Jan 1, 1988·European Journal of Clinical Pharmacology·J WolffK H Tønnesen
Jan 1, 1973·Acta Pharmacologica Et Toxicologica·G Paalzow, L Paalzow
Sep 1, 1971·The Tohoku Journal of Experimental Medicine·K ShimomuraH Tsukamoto
Jun 1, 1968·British Journal of Pharmacology and Chemotherapy·B M CoxO H Osman
Sep 1, 1995·Journal of Pharmacological and Toxicological Methods·L LangermanG J Grant
Oct 1, 1994·Clinical Pharmacology and Therapeutics·W J Jusko, H C Ko
Jan 1, 1994·Life Sciences·A W LipkowskiS K Szyfelbein
Aug 1, 1993·Journal of Pharmacokinetics and Biopharmaceutics·N L DaynekaW J Jusko
Aug 1, 1993·Clinical Pharmacology and Therapeutics·R OsborneM Slevin
Dec 1, 1995·Journal of Pharmacokinetics and Biopharmaceutics·D M Ouellet, G M Pollack
May 15, 1997·Biochemical Pharmacology·D M Ouellet, G M Pollack
Mar 1, 1964·The Journal of Pharmacy and Pharmacology·E J ARIUENS, A M SIMONIS

❮ Previous
Next ❯

Citations

Oct 30, 2008·European Journal of Clinical Pharmacology·Janet K CollerAndrew A Somogyi
May 24, 2005·Journal of Pain and Symptom Management·Jörn Lötsch
May 24, 2005·Journal of Pain and Symptom Management·Jörn Lötsch
Jun 7, 2005·Neurotoxicology·Tsukasa SakuradaShinobu Sakurada
Dec 30, 1998·Pharmacology & Toxicology·M GårdmarkM Hammarlund-Udenaes
Nov 8, 2008·The AAPS Journal·Emily O Dumas, Gary M Pollack
Feb 21, 2006·British Journal of Clinical Pharmacology·Glynn A MorrishAndrew A Somogyi
Jun 24, 2006·Toxicology Letters·Joakim J StrandbergHenrik Druid
Apr 12, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Eva SverrisdóttirMads Kreilgaard
Jun 29, 2005·Pain·Carsten SkarkeJörn Lötsch
Nov 7, 2016·Clinical Pharmacokinetics·Astrid W OostenRon H J Mathijssen
Oct 7, 2006·Current Opinion in Anaesthesiology·Jörn Lötsch
Dec 26, 2008·Clinical Pharmacology and Therapeutics·L E FribergM O Karlsson
Mar 25, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Yaping JiRichard J Traub

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.