Related Experiment Video

Updated: Oct 19, 2026

Gastrointestinal Motility Monitor (GIMM)
08:15

Gastrointestinal Motility Monitor (GIMM)

Published on: December 1, 2010

Agmatine inhibited tolerance to and dependence on morphine in guinea pig ileum in vitro

J Li1, X Li, G Pei

  • 1Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.

Zhongguo Yao Li Xue Bao = Acta Pharmacologica Sinica
|August 7, 1999
PubMed
Abstract

Insights

Agmatine prevents morphine tolerance and dependence in guinea pig ileum muscle. This effect is mediated by imidazoline receptors, offering potential therapeutic insights.

Area of Science:

  • Pharmacology
  • Neuroscience

Background:

  • Morphine (Mor) is a potent opioid analgesic with significant side effects including tolerance and dependence.
  • Opioid-induced tolerance and dependence are complex phenomena involving adaptive changes in the nervous system.
  • Agmatine (Agm), an endogenous amine, has shown neuromodulatory effects.

Purpose of the Study:

  • To investigate the effect of agmatine (Agm) on the development of tolerance to and physical dependence on morphine (Mor) in an in vitro model.
  • To elucidate the potential role of imidazoline receptors in agmatine's modulatory effects on morphine.

Main Methods:

  • Experiments were conducted using the guinea pig ileum longitudinal muscle (GPILM) preparation.
  • Electric field stimulation (EFS) was used to induce and measure muscle contractions.
  • Tolerance and dependence were induced by prolonged exposure to morphine, and the effects of agmatine were assessed.

Main Results:

  • Morphine inhibited EFS-induced contractions with an IC50 of 140 nmol.L-1.
  • Eight-hour incubation with morphine induced a 37-fold increase in the IC50 (tolerance) and a contractile response to naloxone (dependence).
  • Co-incubation with agmatine significantly attenuated morphine-induced tolerance and dependence, an effect reversed by idazoxan, suggesting imidazoline receptor involvement.

Conclusions:

  • Agmatine effectively prevented the development of morphine tolerance and dependence in the GPILM model.
  • The findings suggest that agmatine exerts its anti-tolerance and anti-dependence effects through the activation of imidazoline receptors.
  • This study highlights the potential of agmatine as an adjuvant therapy to mitigate opioid-related side effects.

More Related Videos

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats04:11

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats

Published on: November 6, 2018

Related Concept Videos

Analgesia and Pain Management01:25

Analgesia and Pain Management

Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents01:17

Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents

Diarrhea, a condition marked by frequent loose or watery bowel movements, can be triggered by multiple factors such as viral or bacterial infections, food intolerances, anxiety, medications, and digestive disorders. Symptoms may include abdominal pain, bloating, nausea, and cramping. Severe or prolonged diarrhea can lead to complications like electrolyte imbalances, malnutrition, and dehydration if left untreated.
Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down...
Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
Methods for Studying Drug Absorption: In situ01:09

Methods for Studying Drug Absorption: In situ

In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...