The effects of alfentanil and selected narcotic analgesics on the rate of action potential discharge of medullary respiratory neurones in anaesthetized rats

Abstract

1 The effects of intravenous injections of alfentanil, fentanyl, phenoperidine or morphine on respiratory and peak inspiratory air flow rate, the diaphragm electromyogram (EMG), the activity recorded extracellularly from respiratory neurones located in the ventral respiratory group and the cardiovascular system were examined in anaesthetized rats. 2 Alfentanil produced dose-dependent changes in peripheral and central respiratory parameters, which were prevented by naloxone pretreatment. Minimal effects were produced on the cardiovascular system. The bradypnoea was principally due to a prolongation of the inspiratory phase and was accompanied by a comparable decrease in the peak inspiratory air flow rate. 3 Alfentanil prolonged the discharge duration of inspiratory neurones such that it still maintained a strict phase correlation with the diaphragm EMG, but changes in firing frequency were inconsistent and negligible. The action on expiratory neuronal discharge was analogous to that on inspiratory neuronal discharge but delayed in onset. 4 Hypotension produced by morphine limited the dose used but the respiratory responses to morphine and other selected narcotic analgesics were otherwise similar to that of alfentanil, differing mainly in time-course and magnitude. From the respiratory parameters assessed, the order ofduration of effect was morphine > phenoperidine > fentanyl > alfentanil and the relative potencies were 0.1, 0.5, 2.5 and 1 respectively. 5 The selective prolongation of inspiration and the immediate action on inspiratory neurones suggests that systemically administered narcotic analgesics may alter the mechanisms within the central respiratory rhythm generator which determine the cessation of inspiration.

Biochemical, Oxidative, and Physiological Changes Caused by Acute Exposure of Fentanyl and Its 3 Analogs in Rodents

“…Our results are in agreement with several previous reports where a decrease in RR was observed after fentanyl treatment. 14,45 In one of our recent studies, fentanyl and its analogs 2 , 5 , and 6 were also found to decrease respiratory frequency and cause respiratory depression following inhalation of smoke of these compounds in a static exposure assembly. 46 All μ-opioid receptor agonists, including fentanyl, produce dose-dependent respiratory depression.…”

CrossTalk opposing view: The pre‐Bötzinger complex is not essential for respiratory depression following systemic administration of opioid analgesics

“…These effects are accompanied by prolongation of discharges in inspiratory VRC neurons and prolongation of diaphragmatic EMG activity. The prolongation of inspiration is linked to effects on respiratory phase‐terminating neurons (Fone & Wilson, ), which are widely distributed in the bulbar respiratory network (Ezure, ).…”

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist

“…Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO2/pH chemosensitivity. respiratory neuron discharges; burst and oscillation patterns; opioid actions, bursts and oscillations; opioid lowers respiratory neuron discharge threshold NEURONS in the dorsolateral pons and ventral respiratory column (VRC) of the medulla exhibit a three-phase rhythm and modulate tidal volume in human and nonhuman mammals (38,39,44), and several studies have demonstrated how opiates affect VRC and pontine respiratory neuron rhythm and excitability (11,16,18,20,26,29,31,32,36,48,51). Low doses of opiates withor ␦-receptor affinity slow respiratory frequency, with lesser effects on depth of respiration in humans (9,10,14,47) and cats (26,28).…”