Methylnaloxone suppresses the development of withdrawal syndrome in morphine-dependent rats.

摘要

We studied the effect of peripheral opioid receptor antagonist methylnaloxone on the development of withdrawal syndrome in morphine-dependent rats. Intraperitoneal injections of methylnaloxone iodide in a daily dose of 2 mg/kg over 3 days after morphine withdrawal reduced the severity of withdrawal symptoms. The mean total score of withdrawal syndrome in treated rats (3.20 +/- 0.13) was 2-fold lower compared to the control, mainly due to less pronounced wet dog shake behavior, limb and head shakes, dyspnea, ptosis, and teeth chattering. Methylnaloxone iodide in the specified dose had no effect on such symptoms of withdrawal syndrome as diarrhea and writhing. Our results indicate that modulation of the peripheral opioid system can reduce the severity of opioid withdrawal syndrome. Methylnaloxone-induced variations in the function of peripheral opioid receptors are probably accompanied by changes in the central nervous system, which prevents the development of withdrawal syndrome.