Stimulation of Phrenic nerve activity by an acetylcholine releasing drug: 4-aminopyridine

Abstract

The effect of the acetylcholine releaser 4-aminopyridine on ventilation was studied by recording and quantifying the efferent phrenic nerve activity in 40 paralysed and vagotomized cats; with arterial Po2, PCO2 and pH kept constant. 4-Aminopyridine, given intravenously or in the vertebral artery, stimulates the phrenic nerve activity in a dose dependent manner. The stimulatory effects of 4-aminopyridine on the phrenic nerve activity could be abolished completely by administration of high doses of atropine. We conclude that 4-aminopyridine, which is used clinically for the reversal of a neuromuscular block, stimulates the phrenic nerve activity. Since the role of cholinergic mechanisms in the central chemoreception has been well established, the effect on the phrenic nerve activity is most probably by an increased release of acetylcholine at the site of the central chemoreceptors.

4-Aminopyridine Toxicity: a Case Report and Review of the Literature

“…4-AP enhances the release of acetylcholine from nerve endings and has been shown to increase dopamine transmission in rat striatum [3][4][5][6][7]. Furthermore, it is frequently used as an experimental agent to induce seizures.…”

4-Aminopyridine Reverses Saxitoxin (STX)- and Tetrodotoxin (TTX)-Induced Cardiorespiratory Depression in Chronically Instrumented Guinea Pigs

“…The blockade of potassium channels results in a profound alteration in the voltage-dependence of calcium channel activation/inactivation kinetics which allows a greater than normal calcium influx into the presynaptic terminals and ultimately causes an enhanced level of acetylcholine release from the motor nerve terminals. In addition to augmenting neuromuscular transmission, 4-AP is also known to have a respiratory stimulant effect (Folgering et al, 1979), a positive inotropic effect (Yanagisawa and Taira, 1979;Glover, 1981), and a CNS excitant effect (Rutecki et al, 1987).…”

4-Aminopyridine Hydrochloride (Pymadin)

“…Recently, they have been shown to be highly effective in antagonising ketamine-diazepam anaesthesia in monkeys (MARTINEZ-AGUIRRE and CRUL 1979) and, as described later, in humans (AGOSTON et al 1980), although they have little effect against phencyclidine (S. AGOSTON 1980, unpublished work). 4-Aminopyridine also increases the respiratory drive by a central, probably cholinergic, mechanism (SEE et al 1978;FOLGERING et al 1979), and accordingly it stimulates breathing (SHAW anq BENTLEY 1949, 1952VON HAXTHAUSEN 1955;FASTIER and McDoWALL 1958a, b). Its stimulant effect on breathing is evident from the records of Fig.…”