4-Aminopyridine Reversal of Fentanyl-Induced Respiratory Depression in Normocapnic and Hypercapnic Patients

Abstract

Profound postoperative respiratory depression after larger doses of fentanyl was partially reversed by 4-aminopyridine. This reversal was independent of FIO2' suggesting that the response was not dependent upon peripheral chemoreceptor-mediated drive. Similar reversal of fentanyl-induced depression by 4-aminopyridine was observed before surgery in patients breathing 67% nitrous oxide in oxygen. 4-Aminopyridine had no effect on breathing when given alone in the absence of fentanyl to patients breathing 67% nitrous oxide in oxygen before surgery.

Antagonism of d-tubocurarine-induced neuromuscular blockade with a mixture of 4-aminopyridine and neostigmine in man

“…From a study conducted on humans, Sia and Zandstra claim that 4-AP antagonizes respiratory depression after fentanyl. 16 The shortening of apnoea time in our patients is in accordance with those results.…”

Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults

“…More recently, studies in freely behaving rats have confirmed that blockade of potassium channels with several agents (barium, 4-AP, tetraethylammonium) constitutes an efficient strategy to increase genioglossus activity and reverse NREM hypotonia and REM atonia during sleep (5). Previous studies of 4-AP in humans revealed this drug was capable of reversing opioid-related respiratory depression in the postoperative setting (18,19). Furthermore, it is currently prescribed to improve motor functions in people suffering from multiple sclerosis (8), Figure 3.…”

Treatment of opioid overdose: current approaches and recent advances

“…While this work is largely still in the preclinical stage (for a thorough review of the preclinical literature see Imam et al 2020 ), a few clinical reports have examined respiratory stimulants (potassium channel blockers, N-methyl-D-aspartate receptor antagonists, ampakines, and analeptics), albeit with little-to-no evidence of utility during a real-life overdose event. 4-Aminopyridine, a potassium channel blocker, was the first reported to reverse respiratory depression caused by IV fentanyl (Sia and Zandstra 1981 ). However, 4-aminopyridine can have considerable side effects, including dysesthesias and dizziness (Blight and Henney 2009 ; Hayes et al 2003 ).…”