The ability of Ibutropin to blunt fentanyl-induced respiratory depression is independent of its activation of carotid body chemoafferents DOI Creative Commons

Paulina M. Getsy,

Walter J. May,

Gregory A. Coffee

et al.

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2024, Volume and Issue: 392(2), P. 100060 - 100060

Published: Dec. 10, 2024

This study examined the effects of intravenous injection isobutyric tropine ester (Ibutropin) on ventilation in freely-moving sham-operated (SHAM) male Sprague Dawley rats and those with bilateral carotid sinus nerve transection (CSNX). also a subsequent fentanyl ventilatory parameters both groups rats. Ibutropin (200 μmol/kg, i.v.) elicited rapid pronounced increases breathing frequency, tidal volume, minute ventilation, peak inspiratory expiratory flows, drives SHAM rats, but substantially smaller responses CSNX The (75 μg/kg, similar Ibutropin-treated markedly different changes end-inspiratory end-expiratory pauses, delay, apneic pause. Moreover, fentanyl-induced were than that pre-injected vehicle (saline) rather Ibutropin. These novel findings suggest acts at body-chemoafferent complex to drive by mechanisms may involve entry this cell-permeant into chemoafferent terminals and/or primary glomus cells. A key finding was ability blunt adverse does not require functional body chemoreceptor afferent input brainstem structures controlling breathing. As such, greatly diminish actions within central respiratory control centers peripheral other bodies. SIGNIFICANCE STATEMENT: revealed depressant present

Language: Английский

Nitrosyl factors play a vital role in the ventilatory depressant effects of fentanyl in freely moving guinea pigs DOI Open Access

Paulina M. Getsy,

Walter J. May,

Fraser Henderson

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117847 - 117847

Published: Jan. 24, 2025

Language: Английский

Citations

0
Comparison of fentanyl-induced brain oxygen responses following intravenous and intraperitoneal injections in rats DOI

Feonil G Limiac,

Michael R. Noya,

Eugene A. Kiyatkin

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110412 - 110412

Published: March 1, 2025

Language: Английский

Citations

0
Xylazine Exacerbates Fentanyl-Induced Respiratory Depression and Bradycardia DOI Creative Commons
Catherine Demery‐Poulos, Sierra C. Moore, Erica S. Levitt

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

ABSTRACT Fatal opioid overdoses in the United States have nearly tripled during past decade, with greater than 92% involving a synthetic like fentanyl. Fentanyl potently activates μ-opioid receptor to induce both analgesia and respiratory depression. The danger of illicit fentanyl has recently been exacerbated by adulteration xylazine, an α2-adrenergic agonist typically used as veterinary anesthetic. In 2023, over 1,000% increase xylazine-positive was reported some regions U.S. Xylazine shown potentiate lethality mice, yet mechanistic underpinning for this effect not defined. Herein, we evaluate fentanyl, their combination whole-body plethysmography (to measure respiration) pulse oximetry blood oxygen saturation heart rate) male female CD-1 mice. We show that xylazine decreases breathing rate more increasing expiration time. contrast, primarily reduces inhibiting inspiration, exacerbates these effects. but decreased saturation, when combined, did change maximum level fentanyl-induced hypoxia. also reduced Finally, loss correlated frequency apneas, rate. Together, findings provide insight into how addition may risk overdose. Graphical Abstract

Language: Английский

Citations

1
The ability of Ibutropin to blunt fentanyl-induced respiratory depression is independent of its activation of carotid body chemoafferents DOI Creative Commons

Paulina M. Getsy,

Walter J. May,

Gregory A. Coffee

et al.

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2024, Volume and Issue: 392(2), P. 100060 - 100060

Published: Dec. 10, 2024

This study examined the effects of intravenous injection isobutyric tropine ester (Ibutropin) on ventilation in freely-moving sham-operated (SHAM) male Sprague Dawley rats and those with bilateral carotid sinus nerve transection (CSNX). also a subsequent fentanyl ventilatory parameters both groups rats. Ibutropin (200 μmol/kg, i.v.) elicited rapid pronounced increases breathing frequency, tidal volume, minute ventilation, peak inspiratory expiratory flows, drives SHAM rats, but substantially smaller responses CSNX The (75 μg/kg, similar Ibutropin-treated markedly different changes end-inspiratory end-expiratory pauses, delay, apneic pause. Moreover, fentanyl-induced were than that pre-injected vehicle (saline) rather Ibutropin. These novel findings suggest acts at body-chemoafferent complex to drive by mechanisms may involve entry this cell-permeant into chemoafferent terminals and/or primary glomus cells. A key finding was ability blunt adverse does not require functional body chemoreceptor afferent input brainstem structures controlling breathing. As such, greatly diminish actions within central respiratory control centers peripheral other bodies. SIGNIFICANCE STATEMENT: revealed depressant present

Language: Английский

Citations

1