Inhibition of Nav1.7 channels by methyl eugenol as a mechanism underlying its antinociceptive and anesthetic actions

Abstract

Methyl eugenol is a potential candidate as an effective local anesthetic and analgesic. The antinociceptive and anesthetic effects of methyl eugenol result from the inhibitory action of methyl eugenol on peripheral Na(+) channels.

Methyleugenol Potentiates Central Amygdala GABAergic Inhibition and Reduces Anxiety

“…However, the underlying mechanisms of these functions are still actively being investigated. A previous study reported that ME inhibited the voltage-gated sodium Na V 1.7 channels, which underlies its antinociceptive and anesthetic actions (Wang et al, 2015). Additionally, ME is an agonist of the TRPA1 channel (Moon et al, 2015); blockade or genetic ablation of the TRPA1 channel decreases anxietylike behaviors in mice (de Moura et al, 2014;Lee et al, 2017).…”

“…Indeed, ME was recently reported to counteract anorexigenic signals for feeding regulation in association with GABAergic phasic inhibition in the CeA (Zhu et al, 2018). Other potential cellular targets for ME within the CNS include voltage-gated sodium channels (Wang et al, 2015) and transient receptor potential ankyrin 1 (TRPA1) channels (Moon et al, 2015).…”

Pain transduction: a pharmacologic perspective

“…Interestingly, although TRPV1 and TRPV3 channels share significant homology, TRPV3 channels do not respond to capsaicin or acidic pH [17]. Cutaneous TRPM8 channels are the principle receptors involved in environmental cold sensation and cold pain transduction [13, 19]. …”

“…Significantly, no side effects were observed in these test animals [70]. Another study found that methyl eugenol, an herbal extract, inhibited Nav 1.7 preferentially in both the inactivated and open states [19]. This compound has not been evaluated in animal or human studies as it pertains to induction of analgesia [19].…”

“…Another study found that methyl eugenol, an herbal extract, inhibited Nav 1.7 preferentially in both the inactivated and open states [19]. This compound has not been evaluated in animal or human studies as it pertains to induction of analgesia [19]. Another group studied the effects of selective Nav 1.7 and Nav 1.8 antagonists (ProTxII and A-803467) in mice with osteoarthritis.…”