Reversal of opioid overdose syndrome in morphine-dependent rats using buprenorphine

• Buprenorphine can recover signs/symptoms of methadone overdose in dependent rats.
• Risk of development of withdrawal is less with buprenorphine compared to naloxone.
• 6 mg/kg dose was the best dose that kept rats symptom-free and did not cause withdrawal.
• Possible therapeutic effects of buprenorphine in humans should be evaluated.

The method of choice for reversal of opioid-toxicity is administration of naloxone. This treatment can be accompanied by complications including acute lung-injury, myocardial infarction, or withdrawal-syndrome (in dependent-patients). We aimed to evaluate the efficacy of buprenorphine in reversal of opioid-overdose syndrome in dependent-rats. A prospective case-control study was designed, in which a total of 30 rats were put on opioid-dependency protocol with 10 mg/kg of intra-peritoneal morphine twice daily for 10 days. After confirmation of dependency by naloxone administration, the rats were overdosed by giving 16 mg/kg of intra-peritoneal methadone. They were divided into four groups receiving naloxone (n = 7; 2 mg/kg) and buprenorphine(n = 8, 8, and 7 with doses of 3 mg/kg, 6 mg/kg, and 10 mg/kg), respectively. These four groups were compared regarding reversal of opioid signs/symptoms and development of withdrawal-syndrome. Rats in the first group showed signs/symptoms of opioid-withdrawal severely and with a higher frequency (P < 0.001). In the groups 2–4, all doses recovered the intoxicated-rats without inducing signs/symptoms of withdrawal; however, the 3 mg/kg dose reversed toxicity slower (P < 0.001) and one rat in this group died later due to the re-development of signs of toxicity. Buprenorphine recovers opioid-overdose in morphine-dependent rats and bypasses the withdrawal-syndrome due to administration of naloxone.