Reversal and Prevention of the Respiratory-Depressant Effects of Heroin by the Novel µ-Opioid Receptor Antagonist Methocinnamox in Rhesus Monkeys.
J Pharmacol Exp Ther
; 368(2): 229-236, 2019 02.
Article
en En
| MEDLINE
| ID: mdl-30463875
ABSTRACT
One consequence of the ongoing opioid epidemic is a large number of overdose deaths. Naloxone reverses opioid-induced respiratory depression; however, its short duration of action limits the protection it can provide. Methocinnamox (MCAM) is a novel opioid receptor antagonist with a long duration of action. This study examined the ability of MCAM to prevent and reverse the respiratory-depressant effects (minute volume [VE]) of heroin in five monkeys. MCAM (0.32 mg/kg) was given before heroin to determine whether it prevents respiratory depression; heroin dose-effect curves were generated 1, 2, 4, and 8 days later, and these effects were compared with those of naltrexone (0.032 mg/kg). Heroin dose dependently decreased VE MCAM and naltrexone prevented respiratory depression, shifting the heroin dose-effect curve rightward at least 10-fold. MCAM, but not naltrexone, attenuated these effects of heroin for 4 days. MCAM (0.1-0.32 mg/kg) was given 30 minutes after heroin to determine whether it reverses respiratory depression; heroin dose-effect curves were generated 1, 2, 4, 8, and 16 days later, and these effects were compared with those of naloxone (0.0032-0.1 mg/kg). MCAM and naloxone reversed respiratory depression within 30 minutes, although only MCAM antagonized heroin on subsequent days. Thus, MCAM prevents and reverses respiratory depression, the potentially lethal effect of heroin, longer than opioid receptor antagonists currently in use. Because of its sustained effects, MCAM might provide more effective rescue from and protection against the fatal respiratory-depressant effects of opioids, thereby improving treatment of opioid overdose.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Insuficiencia Respiratoria
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Cinamatos
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Receptores Opioides mu
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Heroína
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Derivados de la Morfina
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Antagonistas de Narcóticos
Límite:
Animals
Idioma:
En
Revista:
J Pharmacol Exp Ther
Año:
2019
Tipo del documento:
Article