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• W4377029122 abstract "<b>Abstract ID 14245</b> <b>Poster Board 68</b> The opioid epidemic remains a major public health challenge, with over 80,000 opioid overdose deaths reported in 2021. Over 70,000 of these deaths involved synthetic opioids, primarily fentanyl and fentanyl analogs such as carfentanil, which is reportedly 100-fold more potent than fentanyl. Highly potent synthetic opioids such as fentanyl and carfentanil are primarily encountered as adulterants of other drugs, most commonly other opioids such as heroin. Some clinical reports suggest that larger doses of naloxone are necessary to reverse overdoses involving carfentanil. As opioid overdose causes death primarily through suppression of ventilation, this study used whole-body plethysmography in rats to determine possible interactions between opioid agonists that might contribute to their apparent increased lethality, in humans. The primary outcome of this study was minute volume (the volume of air ventilated per minute, product of tidal volume and respiratory rate). First, dose-effect curves for the ventilatory depressant effects of fentanyl (0.0056-0.178 mg/kg; i.v.), carfentanil (0.00056-0.0056 mg/kg; i.v.), and heroin (0.178-1.78 mg/kg; i.v.) were determined in male and female Sprague-Dawley rats. Then, dose-effect curves were determined for binary mixtures of <i>mu</i> opioid receptor agonists at three fixed-dose ratios (3:1, 1:1, 1:3) relative to the potency of each drug alone to suppress ventilation to 75% of baseline. Experimentally determined dose-effect curves for opioid agonist mixtures were then compared to the predicted dose-effect curves based on the effects of each drug alone using dose-addition analysis. All opioid agonists dose-dependently reduced minute volume in male and female rats. Fentanyl was significantly more potent at reducing minute volume in females than males, though there was no difference in the potency of carfentanil or heroin across sexes. Fentanyl was 10-fold more potent than heroin in male rats, but 50-fold more potent than heroin in female rats. Carfentanil was approximately 300-fold more potent than heroin in both males and females. Analysis of the effects of agonist mixtures suggests that interactions between the effects of <i>mu</i> opioid receptor agonists on ventilation are simply additive in nature. This study determined the relative potencies of fentanyl, carfentanil, and heroin to suppress ventilation in male and female rats. Observed sex differences in the potency of fentanyl to suppress ventilation warrants further study. Support/Funding Information: Welch Foundation AQ-0039" @default.
• W4377029122 created "2023-05-19" @default.
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• W4377029122 date "2023-05-18" @default.
• W4377029122 modified "2023-09-29" @default.
• W4377029122 title "Ventilatory Effects of<i>M</i><i>u</i>Opioid Receptor Agonist Mixtures" @default.
• W4377029122 doi "https://doi.org/10.1124/jpet.122.142450" @default.
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