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.