Interaction of phenol derivatives with ion channels.

Phenols began to play a prominent role very early in modern operative medicine in the 1860s when Lister introduced his ‘antisepsis’ approach. The treatment of open wounds by carbolic acid dramatically reduced morbidity and mortality of surgical patients for the first time [1]. This central place in operative medicine was lost when, in the early 20th Century, ‘asepsis’ replaced ‘antisepsis’. The powerful antibacterial properties of the phenols have resulted in their derivatives being widely used as stabilizers and preservatives in a huge variety of drug preparations, although this was hardly noticed by clinicians. Certainly, the phenol derivative best known by anaesthetists is propofol, a GABAA agonist and modulator which revolutionized intravenous anaesthesia. The purpose of this editorial is to present current knowledge of the structure–activity relation of phenol derivatives with respect to membrane spanning ion channels and receptors. A substituted benzene ring is the common structural characteristic of a wide variety of pharmacologically active drugs, among them local anaesthetics [2,3] and the general anaesthetic propofol (2,6 diisopropylphenol) (Fig. 1). Other structurally closely related phenol derivatives, such as 4-chloro-m-cresol, ben-zylalcohol and thymol, are in widespread use as bacteriostatic stabilizers in parenteral drug preparations. Naturally occurring phenolicmonoterpenes e.g. thymol, eugenol and carvacrol [4–8] are the active ingredients in the essential oils of plants occurring in the Mediterranean flora. Several beneficial effects have been ascribed to these essential oils, among others their strong bactericidal and antifungal activity [5,9–12] and their anti-inflammatory properties [4,13–15]. In addition, aromatic alcohols with intact phenolic groups and different phenol derivatives have been shown to act as scavengers of reactive oxygen species, thus protecting neurons effectively against oxidative damage and cell death [16]. Although antinociceptive and local anaesthetic effects have long been described for benzylalcohol [17], eugenol and thymol [14], a possible molecular basis for these effects has only recently been