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


CONCLUSIONS
Agm prevented the development of tolerance to and substance dependence on Mor in GPILM in vitro by activation of imidazoline receptors.
Li
J
J
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
Li
X
X
Pei
G
G
Qin
B Y
BY
D000376:Agmatine / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004361:Drug Tolerance; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007093:Imidazoles / Q000037:antagonists & inhibitors; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D011955:Receptors, Drug / Q000037:antagonists & inhibitors
D000701:Analgesics, Opioid; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D000376:Agmatine; D009020:Morphine