Amphetamines modulate fentanyl-depressed respiration in a bidirectional manner.

Autor: Elder HJ; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Varshneya NB; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; Center for Drug Evaluation and Research, Food and Drug Administration, United States Department of Health and Human Services, Silver Spring, MD, USA., Walentiny DM; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Beardsley PM; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; Center for Biomarker Research & Precision Medicine, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA. Electronic address: patrick.beardsley@vcuhealth.org.
Jazyk: angličtina
Zdroj: Drug and alcohol dependence [Drug Alcohol Depend] 2023 Feb 01; Vol. 243, pp. 109740. Date of Electronic Publication: 2022 Dec 16.
DOI: 10.1016/j.drugalcdep.2022.109740
Abstrakt: Background: The opioid epidemic remains one of the most pressing public health crises facing the United States. Fentanyl and related synthetic opioid agonists have largely driven the rising rates of associated overdose deaths, in part, because of their surreptitious use as substitutes for other opioids and as adulterants in psychostimulants. Deaths involving opioids typically result from lethal respiratory depression, and it is currently unknown how co-use of psychostimulants with opioids affects respiratory toxicity. Considering psychostimulant overdoses have increased over 3-fold since 2013, and half of those co-involved opioids, this is a cardinal question.
Methods: Naloxone, d-amphetamine (AMPH), and (±)-methamphetamine (METH) were evaluated for their effects on basal and fentanyl-depressed respiration. Minute volume (MVb) was measured in awake, freely moving mice via whole-body plethysmography to quantify fentanyl-induced respiratory depression and its modulation by dose ranges of each test drug.
Results: Naloxone immediately reversed respiratory depression induced by fentanyl only at the highest dose tested (10 mg/kg). Both AMPH and METH exhibited bidirectional effects on MVb under basal conditions, producing significant (p ≤ 0.05) depressions then elevations of respiration as dose increased. Under depressed conditions the bidirectional effects of AMPH and METH on respiration were exaggerated, exacerbating and then reversing fentanyl-induced depression as dose increased.
Conclusions: These results indicate that co-use of amphetamines with fentanyl may worsen respiratory depression, but conversely, monoaminergic components of the amphetamines may possibly be exploited to mitigate fentanyl overdose.
Competing Interests: Conflict of interest No conflict declared.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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