Pharmacology of viable mechanism agnostic respiratory stimulants for the reversal of drug-induced respiratory depression in humans.

Abstract

INTRODUCTION:

Drug-induced respiratory depression is potentially fatal and can be caused by various drugs such as synthetic opioids and tranquilizers. The only class of respiratory depressants that has a specific reversal agent are opioids, such as naloxone. These reversal agents have limited utility in situations of polysubstance ingestion with agents from multiple respiratory depressant classes. Hence, there is an unmet need for drugs that stimulate breathing irrespective of the underlying cause of respiratory depression, i.e. mechanism agnostic respiratory stimulants.

AREAS COVERED:

In this review, we discuss agnostic respiratory stimulants, tested in humans with promising results, i.e. ampakines, drugs that act at the carotid bodies, N-methyl-D-aspartate receptor antagonist ketamine, and orexin receptor-2-agonist danavorexton, and others that demonstrated positive effects in animals but not yet in humans.

EXPERT OPINION:

Rapid, effective rescuing of individuals who overdosed on respiratory depressants saves lives. While naloxone is the preferred drug for reversing opioid-induced respiratory depression, its effectiveness is limited in cases involving non-opioids. While several agnostic respiratory stimulants showed promise in humans, further research is needed to optimize dosing, evaluate safety and efficacy in deeper respiratory depression (apnea). Additionally, future studies should combine agnostic stimulants with naloxone, to improve rapid, effective rescue from drug overdoses.

• Authors: Maarten van Lemmen, Rutger van der Schrier, Albert Dahan, Monique van Velzen, Elise Sarton, Marieke Niesters
• Journal: Expert opinion on drug metabolism & toxicology (Expert Opin Drug Metab Toxicol) 2023 Jul-Dec Vol. 19 Issue 10 Pg. 671-679 ISSN: 1744-7607 [Electronic] England
• PMID: 37795596 (Publication Type: Journal Article, Review)

Chemical References

• Respiratory System Agents
• Analgesics, Opioid
• Naloxone
• Ketamine
• Narcotic Antagonists

Topics

• Animals
• Humans
• Respiratory System Agents (adverse effects)
• Analgesics, Opioid (adverse effects)
• Naloxone (adverse effects)
• Respiratory Insufficiency (chemically induced, drug therapy)
• Ketamine (adverse effects)
• Drug Overdose (drug therapy)
• Narcotic Antagonists (adverse effects)