Different effects of systemic vs oral methods of prolonged morphine administration on gastrointestinal motility and morphine metabolic pattern in rat

P. K. Janicki, R. Erskine, M. F.M. James

Research output: Contribution to journalArticle

Abstract

The effects of morphine (M) on the gastrointestinal transit (charcoal meal test) and pain response were compared in 2 rat models that had been rendered tolerant to M. Tolerance was induced via the oral route in one group and subcutaneous administration (systemic route) in the other group. M and its metabolite concentrations were also analyzed in plasma and brain tissue of tolerant animals. Despite a similar degree of tolerance to the analgesic effects of M and dependence development (withdrawal syndrome) in both groups, a significant degree of M-induced gastrointestinal inhibition was seen in the oral group after 5 days of oral M treatment but not after prolonged systemic M administration. The tolerance development to the intestinal inhibitory effect of systemic M was furthermore reflected by an increase in the ED50 value for acute administered M in rats treated with M systemically for 5 days (1.64 and 19.7 mg/kg respectively). Significantly less tolerance development to the inhibitory effect of M on intestinal transit was noted in rats drinking M solution for the same period of time. Tolerance ratio for acute gastrointestinal inhibitory effect of M was 12.01 and 1.49 (systemic vs oral M administration respectively). The plasma concentration of an active M metabolite - morphine-6-glucuronide was significantly higher after prolonged oral morphine treatment - no significant differences between two models of tolerance development were noted in brain tissue for M and its metabolites. The observed differences in the drug metabolic profiles of the 2 groups might explain the long-lasting effects of prolonged oral M administration on the gastrointestinal transit.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalResearch Communications in Substances of Abuse
Volume13
Issue number2
StatePublished - Jan 1 1992

Fingerprint

Gastrointestinal Motility
Gastrointestinal Transit
Morphine
Oral Administration
Metabolome
Charcoal
Brain
Drinking
Analgesics
Meals
Pain
Therapeutics
Pharmaceutical Preparations
21-hydroxy-9beta,10alpha-pregna-5,7-diene-3-ol-20-one

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)

Cite this

@article{31899099f20f4066a35bca60ff185a59,
title = "Different effects of systemic vs oral methods of prolonged morphine administration on gastrointestinal motility and morphine metabolic pattern in rat",
abstract = "The effects of morphine (M) on the gastrointestinal transit (charcoal meal test) and pain response were compared in 2 rat models that had been rendered tolerant to M. Tolerance was induced via the oral route in one group and subcutaneous administration (systemic route) in the other group. M and its metabolite concentrations were also analyzed in plasma and brain tissue of tolerant animals. Despite a similar degree of tolerance to the analgesic effects of M and dependence development (withdrawal syndrome) in both groups, a significant degree of M-induced gastrointestinal inhibition was seen in the oral group after 5 days of oral M treatment but not after prolonged systemic M administration. The tolerance development to the intestinal inhibitory effect of systemic M was furthermore reflected by an increase in the ED50 value for acute administered M in rats treated with M systemically for 5 days (1.64 and 19.7 mg/kg respectively). Significantly less tolerance development to the inhibitory effect of M on intestinal transit was noted in rats drinking M solution for the same period of time. Tolerance ratio for acute gastrointestinal inhibitory effect of M was 12.01 and 1.49 (systemic vs oral M administration respectively). The plasma concentration of an active M metabolite - morphine-6-glucuronide was significantly higher after prolonged oral morphine treatment - no significant differences between two models of tolerance development were noted in brain tissue for M and its metabolites. The observed differences in the drug metabolic profiles of the 2 groups might explain the long-lasting effects of prolonged oral M administration on the gastrointestinal transit.",
author = "Janicki, {P. K.} and R. Erskine and James, {M. F.M.}",
year = "1992",
month = "1",
day = "1",
language = "English (US)",
volume = "13",
pages = "167--176",
journal = "Research Communications in Substances of Abuse",
issn = "0193-0818",
publisher = "PJD Publications Ltd",
number = "2",

}

TY - JOUR

T1 - Different effects of systemic vs oral methods of prolonged morphine administration on gastrointestinal motility and morphine metabolic pattern in rat

AU - Janicki, P. K.

AU - Erskine, R.

AU - James, M. F.M.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - The effects of morphine (M) on the gastrointestinal transit (charcoal meal test) and pain response were compared in 2 rat models that had been rendered tolerant to M. Tolerance was induced via the oral route in one group and subcutaneous administration (systemic route) in the other group. M and its metabolite concentrations were also analyzed in plasma and brain tissue of tolerant animals. Despite a similar degree of tolerance to the analgesic effects of M and dependence development (withdrawal syndrome) in both groups, a significant degree of M-induced gastrointestinal inhibition was seen in the oral group after 5 days of oral M treatment but not after prolonged systemic M administration. The tolerance development to the intestinal inhibitory effect of systemic M was furthermore reflected by an increase in the ED50 value for acute administered M in rats treated with M systemically for 5 days (1.64 and 19.7 mg/kg respectively). Significantly less tolerance development to the inhibitory effect of M on intestinal transit was noted in rats drinking M solution for the same period of time. Tolerance ratio for acute gastrointestinal inhibitory effect of M was 12.01 and 1.49 (systemic vs oral M administration respectively). The plasma concentration of an active M metabolite - morphine-6-glucuronide was significantly higher after prolonged oral morphine treatment - no significant differences between two models of tolerance development were noted in brain tissue for M and its metabolites. The observed differences in the drug metabolic profiles of the 2 groups might explain the long-lasting effects of prolonged oral M administration on the gastrointestinal transit.

AB - The effects of morphine (M) on the gastrointestinal transit (charcoal meal test) and pain response were compared in 2 rat models that had been rendered tolerant to M. Tolerance was induced via the oral route in one group and subcutaneous administration (systemic route) in the other group. M and its metabolite concentrations were also analyzed in plasma and brain tissue of tolerant animals. Despite a similar degree of tolerance to the analgesic effects of M and dependence development (withdrawal syndrome) in both groups, a significant degree of M-induced gastrointestinal inhibition was seen in the oral group after 5 days of oral M treatment but not after prolonged systemic M administration. The tolerance development to the intestinal inhibitory effect of systemic M was furthermore reflected by an increase in the ED50 value for acute administered M in rats treated with M systemically for 5 days (1.64 and 19.7 mg/kg respectively). Significantly less tolerance development to the inhibitory effect of M on intestinal transit was noted in rats drinking M solution for the same period of time. Tolerance ratio for acute gastrointestinal inhibitory effect of M was 12.01 and 1.49 (systemic vs oral M administration respectively). The plasma concentration of an active M metabolite - morphine-6-glucuronide was significantly higher after prolonged oral morphine treatment - no significant differences between two models of tolerance development were noted in brain tissue for M and its metabolites. The observed differences in the drug metabolic profiles of the 2 groups might explain the long-lasting effects of prolonged oral M administration on the gastrointestinal transit.

UR - http://www.scopus.com/inward/record.url?scp=0026668728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026668728&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0026668728

VL - 13

SP - 167

EP - 176

JO - Research Communications in Substances of Abuse

JF - Research Communications in Substances of Abuse

SN - 0193-0818

IS - 2

ER -