• Zheng Yong, Xiang Gao, Wentao Ma, Huajing Dong, Zehui Gong, and Ruibin Su.
• Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Beijing 100850, China.
• Eur. J. Pharmacol. 2014 Sep 5; 738: 153-7.

AbstractReversing 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.Copyright © 2014 Elsevier B.V. All rights reserved.

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