Inhibition by general anesthetic propofol of compound action potentials in the frog sciatic nerve and its chemical structure.

Although the intravenous general anesthetic propofol (2,6-diisopropylphenol) has an ability to inhibit nerve conduction, this has not been fully examined. Various agents inhibit compound action potentials (CAPs) in a manner dependent on their chemical structures. To determine propofol's chemical structure that is important in nerve conduction inhibition, we examined the effects of propofol and its related compounds on fast-conducting CAPs recorded from the frog sciatic nerve by using the air-gap method. Propofol concentration-dependently reduced the peak amplitude of the CAP with a half-maximal inhibitory concentration (IC50) value of 0.14 mM. A similar inhibition was produced by other phenols, 4-sec-butylphenol and 4-amylphenol (IC50 values: 0.33 and 0.20 mM, respectively). IC50 values for these and more phenols (4-isopropylphenol, 4-tert-butylphenol, and 4-ter-amylphenol; data published previously) were correlated with the logarithm of their octanol-water partition coefficients. A phenol having ketone group (raspberry ketone) and alcohols (3-phenyl-1-propanol and 2-phenylethylalcohol) inhibited CAPs less effectively than the above-mentioned phenols. The local anesthetic (LA) benzocaine reduced CAP peak amplitudes with an IC50 of 0.80 mM, a value larger than that of propofol. When compared with other LAs, propofol activity was close to those of ropivacaine, levobupivacaine, and pramoxine, while benzocaine activity was similar to those of cocaine and lidocaine. It is concluded that propofol inhibits nerve conduction, possibly owing to isopropyl and hydroxyl groups bound to the benzene ring of propofol and to its lipophilicity; propofol's efficacy is comparable to those of some LAs. These results could serve to develop propofol-related agents exhibiting analgesia when applied topically.

Hinokitiol inhibits compound action potentials in the frog sciatic nerve.

Hinokitiol (ß-thujaplicin) is a natural tropolone derivative contained in Chamaecyparis taiwanensis that has various actions including anti-inflammatory activities. Various plant-derived compounds inhibit compound action potentials (CAPs) in a manner dependent on the chemical structure of the compounds; however, the effects of hinokitiol on nerve conduction have not been examined. To determine whether hinokitiol inhibits CAPs and, if so, the chemical structure of hinokitiol that is important in this inhibition, we examined the effects of hinokitiol and its related compounds on fast-conducting CAPs using the frog sciatic nerve and the air-gap method. Hinokitiol concentration-dependently reduced the peak amplitude of CAPs with a half-maximal inhibitory concentration (IC50) value of 0.54mM. A stereoisomer of hinokitiol, γ-thujaplicin, also inhibited CAPs. Although hinokitiol has hydroxyl, carbonyl and isopropyl groups, all of which are bound to its seven-membered ring, tropolone, which lacks the isopropyl group, had no effects on CAPs. Moreover, CAPs were unaffected by kojic acid, which lacks an isopropyl group, and also by guaiazulene, which has an isopropyl group but not carbonyl or hydroxyl groups. Biosol and 4-isopropylphenol, which have isopropyl and hydroxyl groups bound to their six-membered ring, reduced CAP peak amplitudes. This 4-isopropylphenol's activity was more effective than 4-isopropylcyclohexanol and phenol, and less effective than 4-tert-butylphenol and 4-tert-amylphenol; isopropylbenzene had no effects on CAPs. These results indicate that hinokitiol inhibits frog CAPs, possibly through interaction involving its isopropyl, carbonyl and hydroxyl groups. Hinokitiol, therefore, has an ability to inhibit nerve conduction, which contributes partly to the pharmacological actions of hinokitiol.