title: Nalmefene reverses carfentanil-induced loss of righting reflex and respiratory depression in rats.
abstract: Reversing the respiratory depression induced by carfentanil involves intravenous administration of naloxone or naltrexone, but this treatment has disadvantages. Hence, finding a more appropriate treatment to counter the depressive actions of carfentanil is needed. In the present study, with the naloxone as a control, we investigated the efficacy of nalmefene for countering the depressive actions of carfentanil. Rats were treated successively with carfentanil (10 μg/kg, i.v.) and nalmefene (9.4-150.0 μg/kg, i.m.), and the duration of loss of righting reflex (LORR) recorded. Respiratory parameters were measured in free-moving rats using a whole-body plethysmograph after rats were administered carfentanil (20 μg/kg, i.v.) and nalmefene (9.4-150.0 μg/kg, i.m.) sequentially. The parameters of arterial blood gases were also examined. Nalmefene (9.4-150.0 μg/kg, i.m.) treatment dose-dependently decreased the duration of carfentanil-induced LORR. The respiratory rate after 60 min of nalmefene (150.0 μg/kg, i.m.) treatment increased from 34.3 ± 5.3 bursts/min to 117.8 ± 18.9 bursts/min, and enhanced pause decreased from 1.1 ± 0.1 to 0.4 ± 0.1, and was close to those of normal rats. Furthermore, nalmefene (37.5-150.0 μg/kg) treatment could enable the PaO2, SaO2 and PaCO2 to approach normal levels 10 min (15 min after carfentanil injection) or 30 min (25 min after carfentanil injection) after injection. While, a single injection of naloxone (150.0 μg/kg, i.m.) only achieved partial remission of respiratory depression. These data suggest that nalmefene more effectively counters the depressive actions induced by carfentanil and is a more appropriate treatment to antagonize carfentanil toxicity compared with naloxone.
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yong
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Ma
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Huajing
authors.initials: H
authors.lastname: Dong
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Zehui
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Beijing 100850, China. Electronic address: ruibinsu@126.com.
authors.forename: Ruibin
authors.initials: R
authors.lastname: Su
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D000818:Animals; D001784:Blood Gas Analysis; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D057897:Reflex, Righting / Q000187:drug effects*; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009271:Naltrexone; C017114:carfentanil; C038981:nalmefene; D005283:Fentanyl
keywords: Carfentanil (PubChem CID: 62156); Nalmefene (PubChem CID: 5284594)