Table 2.

Summary of recent findings on pharmacological interventions to prevent fentanyl-induced respiratory depression.

Drug	Route of administration	Pharmacological target	Subjects	Paradigm (fentanyl dose, model)	Main findings	References
A85380	SC	α4β2 nicotinic acetylcholine receptor	Male and female Sprague-Dawley rats	20 μg/kg, IV	Co-administration of A85380 (0.06 mg/kg) and fentanyl or remifentanil markedly reduces respiratory depression and apnea and enhances fentanyl-induced analgesia	Ren et al. [112]
D-amphetamine	IV	Dopamine D1 receptor	Male and female Sprague-Dawley rats	55 μg/kg, IV	D-amphetamine attenuates respiratory acidosis, increases arterial oxygenation, and accelerates the return of consciousness in the setting of fentanyl intoxication	Moody et al. [109]
LY2828360	IP	G protein-biased cannabinoid CB2 receptor	Wildtype and CB2 knockout mice	0.2 mg/kg, IP	Combination of CB2 agonist and fentanyl may represent a safer adjunctive therapeutic strategy compared with a narcotic analgesic alone by attenuating the development of opioid-induced respiratory depression	Zavala et al. [110]
Calabadion 1	IV	Acyclic cucurbit[n]uril molecular container	Male Sprague-Dawley rats	12.5 or 25 μg/kg, IV	Calabadion 1 selectively and dose-dependently reverses the respiratory and central nervous system side-effects of fentanyl	Thevathasan et al. [111]
Oxytocin and WAY-267464	IP	Oxytocin receptor	Male Sprague-Dawley rats	60 nmol/kg, IV	Without vasopressin 1A receptor cross-activation, peptide and non-peptide agonist activation of oxytocin receptors (oxytocin and WAY-267464) rescue fentanyl-induced respiratory depression	Brackley et al. [113]
Methocinnamox	IV and SC	μ-Opioid receptor	Male Sprague-Dawley rats	0.0032–0.178 mg/kg, IV	Methocinnamox reverses and prevents fentanyl-induced antinociception and respiratory depression	Jimenez et al. [96]

IP, intraperitoneal; IV, intravenous; SC, subcutaneous.