title: Reversal of opioid overdose syndrome in morphine-dependent rats using buprenorphine.
abstract: 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 3mg/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.
authors.affiliation: Department of Clinical Toxicology, Loghman-Hakim Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Excellent Center of Clinical Toxicology, Ministry of Health and Medical Education, Tehran, Iran.
authors.forename: Nasim
authors.initials: N
authors.lastname: Zamani
authors.affiliation: Department of Clinical Toxicology, Loghman-Hakim Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Excellent Center of Clinical Toxicology, Ministry of Health and Medical Education, Tehran, Iran. Electronic address: Hassanian@sbmu.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Hassanian-Moghaddam
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Amir Hossein
authors.initials: AH
authors.lastname: Bayat
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
authors.affiliation: Department of Clinical Toxicology, Loghman-Hakim Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Excellent Center of Clinical Toxicology, Ministry of Health and Medical Education, Tehran, Iran.
authors.forename: Shahin
authors.initials: S
authors.lastname: Shadnia
authors.affiliation: Department of Clinical Toxicology, Loghman-Hakim Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Excellent Center of Clinical Toxicology, Ministry of Health and Medical Education, Tehran, Iran.
authors.forename: Mitra
authors.initials: M
authors.lastname: Rahimi
authors.affiliation: Department of Clinical Toxicology, Loghman-Hakim Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Excellent Center of Clinical Toxicology, Ministry of Health and Medical Education, Tehran, Iran.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Hashemi Demaneh
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Nasim
authors.initials: N
authors.lastname: Assar
mesh_terms: D000818:Animals; D002047:Buprenorphine / Q000627:therapeutic use*; D062787:Drug Overdose / Q000188:drug therapy*; D008297:Male; D008691:Methadone / Q000009:adverse effects*; D009021:Morphine Dependence; D009270:Naloxone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone; D002047:Buprenorphine; D008691:Methadone
keywords: Buprenorphine; Methadone toxicity; Naloxone; Opioid overdose; Withdrawal