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

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Abstract

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.

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Abbreviations

CAP:

Compound action potential

IC50 :

Half-maximal inhibitory concentration

Kow :

Octanol-water partition coefficient

LA:

Local anesthetic

nH :

Hill coefficient

TRPA1:

Transient receptor potential ankyrin-1

TRPV1:

Transient receptor potential vanillioid-1

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Funding

This research was partly supported by JSPS KAKENHI, grant number 15 K08673.

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Authors and Affiliations

  1. Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Nobuya Magori, Tsugumi Fujita, Kotaro Mizuta & Eiichi Kumamoto

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  1. Nobuya Magori
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  2. Tsugumi Fujita
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  3. Kotaro Mizuta
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  4. Eiichi Kumamoto
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Correspondence to Eiichi Kumamoto.

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This study was approved by the Animal Care and Use Committee of Saga University, Saga, Japan.

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Magori, N., Fujita, T., Mizuta, K. et al. Inhibition by general anesthetic propofol of compound action potentials in the frog sciatic nerve and its chemical structure. Naunyn-Schmiedeberg's Arch Pharmacol 392, 359–369 (2019). https://doi.org/10.1007/s00210-018-01596-w

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