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Agmatine inhibited tolerance to and dependence on morphine in guinea pig ileum in vitro
1Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
Aim:
To observe effect of agmatine (Agm) on tolerance to and substance dependence on morphine (Mor) in guinea pig ileum longitudinal muscle (GPILM).
Methods:
The experiment was performed in electric field stimulation (EFS) test in vitro.
Results:
Mor inhibited twitch contractions of GPILM induced by EFS [IC50 = 140 (107-182) nmol.L-1]. Incubation of GPILM with Mor 270 nmol.L-1 for 8 h evoked a 37-fold increase in IC50 of Mor (tolerance) and a contractile response to naloxone (Nal, substance dependence). When the preparations were coincubated with Mor + Nal and Mor + Agm, Mor lost the ability to induce tolerance and inhibited the contractile responses of the preparations to Nal by 90% and 75%, respectively. These effects of Agm could be almost completely antagonized by idazoxan.
Conclusion:
Agm prevented the development of tolerance to and substance dependence on Mor in GPILM in vitro by activation of imidazoline receptors.
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.