European Journal of Anaesthesiology

Original Article
(RD) Surgery

Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol

G. Haeseler a1c1, D. Maue a1, J. Grosskreutz a2, J. Bufler a2, B. Nentwig a1, S. Piepenbrock a1, R. Dengler a2 and M. Leuwer a3
a1 Hannover Medical School, Department of Anaesthesiology, Hannover, Germany
a2 Hannover Medical School, Department of Neurology and Neurophysiology, Hannover, Germany
a3 University of Liverpool, University Department of Anaesthesia, Liverpool, UK

Article author query
haeseler g   [PubMed][Google Scholar] 
maue d   [PubMed][Google Scholar] 
grosskreutz j   [PubMed][Google Scholar] 
bufler j   [PubMed][Google Scholar] 
nentwig b   [PubMed][Google Scholar] 
piepenbrock s   [PubMed][Google Scholar] 
dengler r   [PubMed][Google Scholar] 
leuwer m   [PubMed][Google Scholar] 


Background and objective: Thymol is a naturally occurring phenol derivative used in anaesthetic practice as a stabilizer and preservative of halothane, usually at a concentration of 0.01%. Although analgesic effects have long been described for thymol and its structural homologue menthol, a molecular basis for these effects is still lacking. We studied the blocking effects of thymol and menthol on voltage-activated sodium currents in vitro as possible molecular target sites.

Methods: Whole cell sodium inward currents via heterologously (HEK293 cells) expressed rat neuronal (rat type IIA) and human skeletal muscle (hSkM1) sodium channels were recorded in the absence and presence of definite concentrations of either thymol or menthol.

Results: When depolarizing pulses to 0 mV were started from a holding potential of-70 mV, halfmaximum blocking concentrations (IC50) for the skeletal muscle and the neuronal sodium channel were 104 and 149 µmol for thymol and 376 and 571 µmol for menthol. The blocking potency of both compounds increased at depolarized holding potentials with the fraction of inactivated channels. The estimated dissociation constant K d for thymol and menthol from the inactivated state was 22 and 106 µmol for the neuronal and 23 and 97 µmol for the skeletal muscle sodium channel, respectively.

Conclusions: The results suggest that antinociceptive and local anaesthetic effects of thymol and menthol might be mediated via blockade of voltage-operated sodium channels with the phenol derivative thymol being as potent as the local anaesthetic lidocaine.

(Published Online August 16 2006)
(Accepted January 2002)

Key Words: anti-infective agents; local; thymol; chlorhexanols; menthol; ion channels; sodium channel; terpenes; menthol; thymol.

c1 Correspondence to: Gertrud Haeseler, Department of Anaesthesiology, OE8050, Hannover Medical School, D-30623 Hannover, Germany. E-mail:; Tel: +49 511 532 2070; Fax: +49 511 532 5649