Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids

Hall, Alex R.; Turcotte, Carolyn M.; Betts, Brooke A.; Yeung, Wing-Yee; Agyeman, Abena S.; Burk, Lâle Aka

doi:10.1016/j.ejphar.2004.10.026

Cited by 135 publications

(120 citation statements)

References 30 publications

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“…In addition, menthol is known to be a potent positive modulator of the -aminobutyric acid type A (GABA A ) receptor [20] and acts as a potent positive allosteric modulator of GABA A receptors via sites similar to propofol, an intravenous anesthetic agent [21]. These finding suggest a possibility that menthol has an anesthetic effect on fish as well as sea cucumber and prawns [3,4].…”

Section: Introductionmentioning

confidence: 92%

“…This was proved when they craved to swim towards the food sources [34]. On human GABA A and glycine receptors, menthol isomers act as important targets for modulation by sedative, anxiolytic, and general anesthetic agents [20,35,36]. Menthol reduces the excitation of rat hippocampal neurons not only by enhancing the currents induced at low concentrations of GABA but also by directly activating the GABA A receptor [37].…”

Section: Discussionmentioning

confidence: 99%

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Menthol Induces Surgical Anesthesia and Rapid Movement in Fishes

Kasai¹,

Hososhima²,

Yun-Fei³

2014

TONEURJ

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Abstract:To determine whether fishes respond to menthol, Japanese medaka Oryzias latipes, goldfish Carassius auratus, and zebrafish Danio rerio were exposed to various types of menthol receptors agonists and the behavioral responses to these drugs were observed. Waterbone application of dl-menthol (0.5 mM) induced surgical anesthesia in 100% of medaka, 90% of goldfish, and 100% of zebrafish. The percentage of response increased dose-dependently from 0.2 mM to 0.5 mM. There were no differences in either percentage or latency of the response in surgical anesthesia among dl-, d-, and l-types of menthol. A high (3.0 mM) concentration of any of the three types of menthol induced rapid movement followed by the anesthetic response. Rapid movement was observed with allyl isothiocyanate, a cold nociceptor agonist, but not with icilin, a cold receptor agonist, in medaka and goldfish. Both allyl isothiocyanate and icilin failed to induce surgical anesthesia. To determine the involvement of -aminobutyric acid (GABA) system in menthol-induced surgical anesthesia, the effect of the receptors antagonist for the GABA A was tested. Pretreatment with a specific GABA A receptor antagonist prolonged the latency of the anesthetic response to menthol, but not to cold-water stimulation, in medaka and goldfish. These results demonstrate that menthol can play a role in the induction of surgical anesthesia in fishes, related at least in part to the activation of GABA A receptors, and of rapid movement possibly via cold nociceptors.

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Section: Introductionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Menthol Induces Surgical Anesthesia and Rapid Movement in Fishes

Kasai¹,

Hososhima²,

Yun-Fei³

2014

TONEURJ

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“…In an earlier study, Hall et al (2004) showed that the effect of menthol on GABA A currents were stereoselective, with (1)-menthol being more potent than (2)-menthol, while menthol modulation of glycine receptors did not display stereospecificity. In our study, we could not detect a stereoselectivity of menthol actions on 5-HT 3 receptors (Fig.…”

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confidence: 99%

“…In earlier studies, menthol in the concentration ranges used in this study has been shown to act directly on GABA A (EC 50 5 1.1 mM) (Pan et al, 2012), glycine (100-300 mM) (Hall et al, 2004), and ryanodine receptors (1 mM) (Palade, 1987;Neumann and Copello, 2011). Both ligand-gated and voltagegated channels are inhibited by menthol (IC 50 5 297 mM for Na 1 channels and IC 50 5 125 mM for Ca 21 channels in dorsal horn neurons) (Pan et al, 2012).…”

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confidence: 99%

Menthol Inhibits 5-HT₃Receptor–Mediated Currents

Ashoor

Nordman

Veltri

et al. 2013

J Pharmacol Exp Ther

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The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, were tested on the function of human 5-hydroxytryptamine type 3 (5-HT 3 ) receptors expressed in Xenopus laevis oocytes. 5-HT (1 mM)-evoked currents recorded by two-electrode voltage-clamp technique were reversibly inhibited by menthol in a concentration-dependent (IC 50 5 163 mM) manner. The effects of menthol developed gradually, reaching a steadystate level within 10-15 minutes and did not involve G-proteins, since GTPgS activity remained unaltered and the effect of menthol was not sensitive to pertussis toxin pretreatment. The actions of menthol were not stereoselective as (2), (1), and racemic menthol inhibited 5-HT 3 receptor-mediated currents to the same extent.Menthol inhibition was not altered by intracellular 1,2-bis(oaminophenoxy)ethane-N,N,N9,N9-tetraacetic acid injections and transmembrane potential changes. The maximum inhibition observed for menthol was not reversed by increasing concentrations of 5-HT. Furthermore, specific binding of the 5-HT 3 antagonist [ 3 H]GR65630 was not altered in the presence of menthol (up to 1 mM), indicating that menthol acts as a noncompetitive antagonist of the 5-HT 3 receptor. Finally, 5-HT 3 receptor-mediated currents in acutely dissociated nodose ganglion neurons were also inhibited by menthol (100 mM). These data demonstrate that menthol, at pharmacologically relevant concentrations, is an allosteric inhibitor of 5-HT 3 receptors.

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“…13) Another study using monoterpenes indicated a neuroactive property affecting neuronal intracellular signaling which could be provoked through neurotransmittergated current modulation induced by these terpenes. 14) For these reasons, it appeared possible that (Ϫ)-carvone could also have analgesic activity involving the central and peripheral nervous systems. Therefore our objective was to verify the antinociceptive effect of (Ϫ)-carvone using different experimental models of pain and to investigate whether such effect might be involved in nervous excitability using the single sucrose gap technique.…”

mentioning

confidence: 99%

Antinociceptive Activity of (-)-Carvone: Evidence of Association with Decreased Peripheral Nerve Excitability

Gonçalves

Oliveira

Benedito

et al. 2008

Biological & Pharmaceutical Bulletin

110

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(؊)-Carvone is a monoterpene ketone that is the main active component of Mentha plant species like Mentha spicata. This study aimed to investigate the antinociceptive activity of (؊)-carvone using different experimental models of pain and to investigate whether such effects might be involved in the nervous excitability elicited by others monoterpenes. In the acetic acid-induced writhing test, we observed that (؊)-carvone-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg was administered. It was also demonstrated that (؊)-carvone inhibited the licking response of the injected paw when 100 and 200 mg/kg was administered (i.p.) to mice in the first and second phases of the formalin test. Since naloxone (5 mg/kg, s.c.), an opioid antagonist, showed no influence on the antinociceptive action of (؊)-carvone (100 mg/kg), this suggested nonparticipation of the opioid system in the modulation of pain induced by (؊)-carvone. Such results were unlikely to be provoked by motor abnormality, since (؊)-carvone-treated mice did not exhibit any performance alteration on the Rota-rod apparatus. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and observed that (؊)-carvone (10 mM) was able to reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 50% from control recordings. We conclude that (؊)-carvone has antinociceptive activity associated with decreased peripheral nerve excitability.

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Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids

Cited by 135 publications

References 30 publications

Menthol Induces Surgical Anesthesia and Rapid Movement in Fishes

Menthol Induces Surgical Anesthesia and Rapid Movement in Fishes

Menthol Inhibits 5-HT₃Receptor–Mediated Currents

Antinociceptive Activity of (-)-Carvone: Evidence of Association with Decreased Peripheral Nerve Excitability

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Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids

Cited by 135 publications

References 30 publications

Menthol Induces Surgical Anesthesia and Rapid Movement in Fishes

Menthol Induces Surgical Anesthesia and Rapid Movement in Fishes

Menthol Inhibits 5-HT3Receptor–Mediated Currents

Antinociceptive Activity of (-)-Carvone: Evidence of Association with Decreased Peripheral Nerve Excitability

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Menthol Inhibits 5-HT₃Receptor–Mediated Currents