Presynaptic M1, M2, and A1 receptors play roles in tetanic fade induced by pancuronium or cisatracurium

Abstract

The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine.

<b>Atropine is more efficient than ZM241385 to reduce a drastic level of fade caused by cisatracurium at 50 Hz

“…These data indicate that a higher activation of M 1 receptors on motor nerve by acetylcholine might be occurring in the cisatracurium-induced 100% Fade. It has already been demonstrated that A-value is influenced by presynaptic M 1 receptors activity when the motor nerve is stimulated at 50.00 Hz trains (Oliveira, Timóteo & Sá, 2002 cisatracurium-induced Fade would be the expected effect when the preparations were previously treated with ZM241385 (Oliveira et al, 2002;Pereira et al, 2012), it was supposed that the anticholinesterase activity of cisatracurium (Bornia et al, 2009;Bornia et al, 2011;Pereira et al, 2011) in the experimental condition causing 100% Fade reduced the expression of facilitatory effect induced by the blockade of A 2A receptors by producing a level of M 1 /M 2 activation by acetylcholine higher than that determined by the separate treatment of preparations with cisatracurium. Indeed, the previous treatment of preparations with ZM241385 caused a reduction in the A-value induced by cisatracurium which was not significantly (p > 0.05) different from that obtained after the administration of cisatracurium.…”

“…This effect of atropine might be determined by the ability of the drug to reduce the action of acetylcholine on the presynaptic inhibitory-M 2 muscarinic receptors when the motor nerve is being stimulated at tetanizing frequencies (Prado et al, 1987). On the other hand, it has been shown that cisatracurium, an antinicotinic muscular relaxant agent that exhibits anticholinesterase activity in its molecules at clinical concentration (Bornia et al, 2009), also causes Fade in the phrenic nerve diaphragm muscle preparations of rats, but the Fade caused by the agent is not mediated by presynaptic inhibitory-M 2 receptors. In fact, Fade caused by cisatracurium seems to depend more on the activation of facilitatory-M 1 and facilitatory-A 2A adenosine receptors than on activation of presynaptic inhibitory-M 2 receptors on motor nerve (Bornia et al, 2009;Bornia et al, 2011;Pereira et al, 2012).…”

“…On the other hand, it has been shown that cisatracurium, an antinicotinic muscular relaxant agent that exhibits anticholinesterase activity in its molecules at clinical concentration (Bornia et al, 2009), also causes Fade in the phrenic nerve diaphragm muscle preparations of rats, but the Fade caused by the agent is not mediated by presynaptic inhibitory-M 2 receptors. In fact, Fade caused by cisatracurium seems to depend more on the activation of facilitatory-M 1 and facilitatory-A 2A adenosine receptors than on activation of presynaptic inhibitory-M 2 receptors on motor nerve (Bornia et al, 2009;Bornia et al, 2011;Pereira et al, 2012). Contrastingly, it has been reported that the cisatracurium-induced TOF fade occurs mainly by the activation of M 2 and A 2A receptors caused by acetylcholine released from motor nerve and from the adenosine respectively released from neuronal and muscular sources (Pereira et al, 2012).…”

“…conditions of neuromuscular transmission, as different patterns of stimulation applied on motor nerve in the absence or in the presence of drugs, may modify the autoregulatory cholinergic (facilitatory-nicotinic receptors expressing α3β2 subunits, facilitatory-M 1 and inhibitory-M 2 subtypes of muscarinic receptors) and the modulatory (facilitatory-A 2A and inhibitory-A 1 adenosine receptors) mechanisms on the terminal (Bornia, Bando, Machinsky, Pereira, & Prado, 2009;Pereira, Bornia, Sá, & Prado, 2011). Therefore, the Fade caused by antinicotinic (hexamethonium) agent may be severe (~ 89%) when the concentration of such agent is causing 25% TOF fade (Pereira, Sá, & Prado, 2012).…”

Sugammadex: novos questionamentos sobre a reversão

“…Other mechanisms, besides the blockade of neuronal nicotinic receptors, seem to be involved with the development of fatigue, as shown in muscle-phrenic nerve preparation. Among them, there are the facilitator action of type 1 muscarinic receptors (M1) and/or inhibitory action of type 2 (M2) 9 . In clinical monitoring this fatigue is characterized by TOF < 0.9 2,10,11 .…”