Fentanyl activates opposing opioid and non-opioid receptor systems that control breathing DOI Creative Commons
Santhosh M. Baby,

Walter J. May,

Paulina M. Getsy

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 18, 2024

Fentanyl elicits profound disturbances in ventilatory control processes humans and experimental animals. The traditional viewpoint with respect to fentanyl-induced respiratory depression is that once the effects on frequency of breathing (Freq), tidal volume (TV), minute ventilation (MV = Freq × TV) are resolved, then no longer a concern. results present study challenge this concept findings, as they reveal while apparent inhibitory fentanyl (75 μg/kg, IV) Freq, TV, MV adult male rats were fully resolved within 15 min, many other responses full effect, including opposing timing parameters. For example, although at inspiratory duration (Ti) end pause (EIP) elevated, whereas expiratory (Te) (EEP) diminished. Since TV had subsided it would be expected administration an opioid receptor (OR) antagonist have minimal if parameters resolved. We now report intravenous injection 1.0 mg/kg dose peripherally restricted OR antagonist, methyl-naloxone (naloxone methiodide, NLXmi), did not elicit arousal but elicited some relatively minor changes MV, Te, EEP pronounced Ti EIP. In contrast, 2.5 NLXmi dramatic variables, which associated increases non-apneic events such apneas. two compelling conclusions from follows: 1) blockade central ORs produced by apparently 2) induced activation systems counter-balancing TV: one being system non-OR excitatory system.

Language: Английский

Fentanyl activates opposing opioid and non-opioid receptor systems that control breathing DOI Creative Commons
Santhosh M. Baby,

Walter J. May,

Paulina M. Getsy

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 18, 2024

Fentanyl elicits profound disturbances in ventilatory control processes humans and experimental animals. The traditional viewpoint with respect to fentanyl-induced respiratory depression is that once the effects on frequency of breathing (Freq), tidal volume (TV), minute ventilation (MV = Freq × TV) are resolved, then no longer a concern. results present study challenge this concept findings, as they reveal while apparent inhibitory fentanyl (75 μg/kg, IV) Freq, TV, MV adult male rats were fully resolved within 15 min, many other responses full effect, including opposing timing parameters. For example, although at inspiratory duration (Ti) end pause (EIP) elevated, whereas expiratory (Te) (EEP) diminished. Since TV had subsided it would be expected administration an opioid receptor (OR) antagonist have minimal if parameters resolved. We now report intravenous injection 1.0 mg/kg dose peripherally restricted OR antagonist, methyl-naloxone (naloxone methiodide, NLXmi), did not elicit arousal but elicited some relatively minor changes MV, Te, EEP pronounced Ti EIP. In contrast, 2.5 NLXmi dramatic variables, which associated increases non-apneic events such apneas. two compelling conclusions from follows: 1) blockade central ORs produced by apparently 2) induced activation systems counter-balancing TV: one being system non-OR excitatory system.

Language: Английский

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