Inhibition by general anesthetic propofol of compound action potentials in the frog sciatic nerve and its chemical structure
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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.
KeywordsPropofol Benzocaine Nerve conduction Analgesia Compound action potential Frog sciatic nerve
Compound action potential
Half-maximal inhibitory concentration
Octanol-water partition coefficient
Transient receptor potential ankyrin-1
Transient receptor potential vanillioid-1
This research was partly supported by JSPS KAKENHI, grant number 15 K08673.
Compliance with ethical standards
This study was approved by the Animal Care and Use Committee of Saga University, Saga, Japan.
Conflict of interest
The authors declare that they have no conflicts of interest.
- Catterall WA, Mackie K (2011) Local anesthetics. In: Brunton LL, Chabner BA, Knollmann BC (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 12th edn. McGraw-Hill, Medical Publishing Division, New York, USA, pp 565–582Google Scholar
- ChemIDplus (2017) Bethesda, MD: National Library of medicine (US); [update daily; accessed 2017 October 18]. Available at: https://chem.nlm.nih.gov/chemidplus/
- Fields HL (1987) Pain, McGraw-Hill. USA, New YorkGoogle Scholar
- Kumamoto E, Mizuta K, Fujita T (2012) Peripheral nervous system in the frog as a tool to examine the regulation of the transmission of neuronal information. In: Murray JL (ed) Frogs: biology, ecology and uses. Nova Science Publishers, Inc., New York, pp 89–106Google Scholar
- Martella G, De Persis C, Bonsi P, Natoli S, Cuomo D, Bernardi G, Calabresi P, Pisani A (2005) Inhibition of persistent sodium current fraction and voltage-gated L-type calcium current by propofol in cortical neurons: implications for its antiepileptic activity. Epilepsia 46:624–635CrossRefGoogle Scholar
- Mizuta K, Fujita T, Yamagata H, Kumamoto E (2017) Bisphenol A inhibits compound action potentials in the frog sciatic nerve in a manner independent of estrogen receptors. Biochem Biophys Rep 10:145–151Google Scholar
- Nadeson R, Goodchild CS (1997) Antinociceptive properties of propofol: involvement of spinal cord γ-aminobutyric acidA receptors. J Pharmacol Exp Ther 283:1181–1186Google Scholar
- Shi Q-Q, Sun X, Fang H (2014) A mechanism study on propofol’s action on middle latency auditory evoked potential by neurons in ventral partition of medial geniculate body in rats. Eur Rev Med Pharmacol Sci 18:1859–1868Google Scholar
- Vanable JW (1985) Benzocaine: an excellent amphibian anesthetic. Axolotl Newsletter 14:19–21Google Scholar