olvanil and zingerone

Although capsaicin not only activates transient receptor potential vanilloid-1 (TRPV1) channels but also inhibits nerve conduction, the latter action has not yet been fully examined. The purpose of the present study was to know whether various vanilloids have an inhibitory action similar to that of capsaicin and further to compare their actions with that of local anesthetic procaine.. Fast-conducting compound action potentials (CAPs) were recorded from frog sciatic nerve fibers by using the air-gap method.. Capsaicin reversibly and concentration-dependently reduced the peak amplitude of the CAP. TRPV1 antagonist capsazepine did not affect the capsaicin activity, and powerful TRPV1 agonist resiniferatoxin had no effect on CAPs, indicating no involvement of TRPV1 channels. Capsaicin analogs and other various vanilloids also inhibited CAPs in a concentration-dependent manner. An efficacy sequence of these inhibitions was capsaicin=dihydrocapsaicin>capsiate>eugenol>guaiacol≥zingerone≥vanillin>vanillylamine. Vanillic acid had almost no effect on CAPs; olvanil and curcumin appeared to be effective less than capsaicin. Capsaicin and eugenol were, respectively, ten- and two-fold effective more than procaine in CAP inhibition, while each of guaiacol, zingerone and vanillin was five-fold effective less than procaine.. Various vanilloids exhibit CAP inhibition, the extent of which is determined by the property of the side chain bound to the vanillyl group, and some of them are more effective than procaine. These results may serve to unveil molecular mechanisms for capsaicin-induced conduction block and to develop antinociceptive drugs related to capsaicin.

Topics: Action Potentials; Animals; Antipruritics; Benzaldehydes; Benzylamines; Capsaicin; Curcumin; Diterpenes; Eugenol; Female; Guaiacol; Male; Procaine; Ranidae; Sciatic Nerve; Structure-Activity Relationship; TRPV Cation Channels; Vanillic Acid

Desensitization is a process that describes the diminishing effect of a drug upon repeated applications. In regard to capsaicin, the pungent compound in hot pepper, it is well established that removal of extracellular calcium markedly diminishes desensitization. To explore whether this behavior extends to other analogues of capsaicin, we have determined the effect of removing extracellular calcium with capsaicin analogues, zingerone and olvanil, by whole-cell patch clamping cultured rat trigeminal ganglion neurons. Zingerone, like capsaicin, is pungent but has a shorter acyl chain, whereas olvanil is non-pungent and has a longer acyl chain. The currents evoked by 30-s applications of 30 mM zingerone or 1 microM olvanil repeated every 3 min differ in two important ways from the responses evoked by 1 microM capsaicin under these same conditions. In the presence of extracellular calcium, repeated applications of zingerone and olvanil produce nearly complete desensitization. Also in contrast to capsaicin, removing extracellular calcium for these two agonists does not diminish desensitization. These data analyses suggest the existence of calcium-independent pathways that can result in desensitization, and that pungency is not related to the phenomenon of desensitization.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcium; Capsaicin; Extracellular Space; Guaiacol; Neurons, Afferent; Pain; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Stimulation, Chemical; Tachyphylaxis; Taste; Trigeminal Ganglion