Nalmefene reverses carfentanil-induced loss of righting reflex and respiratory depression in rats

Zheng, Yongchang; Gao, Xiang; Ma, Wentao; Dong, Huajing; Gong, Zhigang; Su, Rui‐Bin

doi:10.1016/j.ejphar.2014.05.044

Cited by 23 publications

(16 citation statements)

References 23 publications

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“…While multiple studies have reported that nalmefene has a higher affinity than naloxone at both native and recombinant m opioid receptors (Emmerson et al, 1994;Toll et al, 1998;Cassel et al, 2005), there is no compelling evidence this translates to a clinically significant advantage in a hospital setting (Glass et al, 1994;Kaplan et al, 1999). However, in a study attempting to model overdose rescue in a nonhospital setting, Yong et al (2014) compared the effects of bolus intramuscular injections of either nalmefene or naloxone to reverse carfentanil-induced loss of righting reflex and respiratory depression. Rats were administered 10 mg/kg of carfentanil (i.v.)…”

Section: Discussionmentioning

confidence: 99%

Fighting Fire with Fire: Development of Intranasal Nalmefene to Treat Synthetic Opioid Overdose

Krieter

Gyaw

Crystal

et al. 2019

J Pharmacol Exp Ther

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The dramatic rise in overdose deaths linked to synthetic opioids (e.g., fentanyl, carfentanil) may require more potent, longerduration opiate antagonists than naloxone. Both the high affinity of nalmefene at m opiate receptors and its long half-life led us to examine the feasibility of developing an intranasal (IN) formulation as a rescue medication that could be especially useful in treating synthetic opioid overdose. In this study, the pharmacokinetic properties of IN nalmefene were compared with an intramuscular (i.m.) injection in a cohort of healthy volunteers. Nalmefene was absorbed slowly following IN administration, with a median time to reach C max (T max) of 2 hours. Addition of the absorption enhancer dodecyl maltoside (Intravail, Neurelis, Inc., Encinitas, CA) reduced T max to 0.25 hour and increased C max by ∼2.2-fold. The pharmacokinetic properties of IN nalmefene (3 mg) formulated with dodecyl maltoside has characteristics consistent with an effective rescue medication: its onset of action is comparable to an i.m. injection of nalmefene (1.5 mg) previously approved to treat opioid overdose. Furthermore, the C max following IN administration was ∼3-fold higher than following i.m. dosing, comparable to previously reported plasma concentrations of nalmefene observed 5 minutes following a 1-mg i.v. dose. The high affinity, very rapid onset, and long half-life (.7 hours) of IN nalmefene present distinct advantages as a rescue medication, particularly against longer-lived synthetic opioids.

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Section: Discussionmentioning

confidence: 99%

Fighting Fire with Fire: Development of Intranasal Nalmefene to Treat Synthetic Opioid Overdose

Krieter

Gyaw

Crystal

et al. 2019

J Pharmacol Exp Ther

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“…Carfentanil, the active ingredient of Wildnil, is a fentanyl analogue that is approved for veterinary use as a tranquilizing agent for sedation, as a hypnotic, and as anesthesia of animals such as elephants, gazelles, goats, horses, pigs, polar bears, rhinoceroses, seals, and wolves [ 23 – 29 ]. It has been extensively studied in animals since it was first synthesized [ 23 , 28 – 30 , 32 , 37 , 38 , 109 ], but a few human studies have been also reported [ 31 , 33 , 34 ]. Carfentanil has been characterized as the most potent, dangerous, and commercially available fentanyl analogue.…”

Section: Carfentanilmentioning

confidence: 99%

“…PET imaging showed that intravenous and intranasal naloxone produced similar decrease in mOR occupancy caused by [ 11 C] carfentanil [ 129 ]. However, naloxone has a shorter duration of action than that of carfentanil, and multiple doses may be needed to reverse carfentanil’s effects [ 38 , 42 , 99 , 111 , 113 , 117 , 130 ]. One or two doses of naloxone are considered enough to treat a heroin overdose.…”

Section: Carfentanilmentioning

confidence: 99%

“…On the other hand, the efficacy of naltrexone in reaching mOR is not as good as that of carfentanil; there is a need to find new opioid antagonists with fewer disadvantages. Yong et al [ 38 ] investigated the efficacy of different doses of nalmefene for antagonizing carfentanil-induced loss of righting reflex and respiratory depression using naloxone as a control in rats. Respiratory parameters and parameters of arterial blood gases were monitored through the procedure.…”

Section: Carfentanilmentioning

confidence: 99%

“…Respiratory parameters and parameters of arterial blood gases were monitored through the procedure. Nalmefene was found to dose-dependently decrease the duration of loss of righting reflex and reverse the respiratory depression caused by carfentanil [ 38 ].…”

Section: Carfentanilmentioning

confidence: 99%

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Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil and carfentanil

et al. 2017

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PurposeOcfentanil and carfentanil are two potent synthetic opioids that are analogues of fentanyl and are actively involved in the recent fentanyl crisis. The aim of this review is to provide all the available information on these two fentanyl analogues.MethodsAll reviewed information was gathered through a detailed search of PubMed and the World Wide Web using relevant keywords.ResultsLike most of the members of the family of fentanyls, they are either sold as heroin to unsuspecting users or used extensively to lace heroin street samples. Despite the fact that ocfentanil was studied clinically in the early 1990s, it did not manage to find its place in clinical practice. On the other hand, carfentanil is mainly used today as an anesthetic agent in large animals. Ocfentanil and carfentanil are used and abused extensively, mainly in Europe and in the United States. As a result, they are the cause of some verified intoxication cases and deaths worldwide. This review provides information concerning chemistry, synthesis, prevalence, pharmacology, and toxicology, as well as the current legal status of these two fentanyl analogues. Analytical methods developed for the determination of ocfentanil and carfentanil in biological specimens and seized materials, as well as related intoxication and lethal cases are also presented.ConclusionsOcfentanil and carfentanil are undeniably very dangerous opioid drugs and a very serious matter of concern for public safety. The authorities should take the appropriate actions to avoid the expansion of this threat by taking proper and prompt measures.

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Fall 52 – Mundbodenkarzinom

Hübler

2022

Mehr Komplikationen in Der Anästhesie

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Nalmefene reverses carfentanil-induced loss of righting reflex and respiratory depression in rats

Cited by 23 publications

References 23 publications

Fighting Fire with Fire: Development of Intranasal Nalmefene to Treat Synthetic Opioid Overdose

Fighting Fire with Fire: Development of Intranasal Nalmefene to Treat Synthetic Opioid Overdose

Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil and carfentanil

Fall 52 – Mundbodenkarzinom

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