Hostname: page-component-76fb5796d-9pm4c Total loading time: 0 Render date: 2024-04-26T05:07:12.226Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of ifenprodil on voltage-gated tetrodotoxin-resistant Na+ channels in rat sensory neurons

Published online by Cambridge University Press:  01 September 2007

S. Tanahashi ,
H. Iida ,
A. Oda ,
Y. Osawa ,
M. Uchida  and
S. Dohi
S. Tanahashi
Affiliation:
Gifu University Graduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu City, Gifu, Japan
H. Iida
Affiliation:
Gifu University Graduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu City, Gifu, Japan
A. Oda
Affiliation:
Gifu University Graduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu City, Gifu, Japan
Y. Osawa
Affiliation:
Gifu University Graduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu City, Gifu, Japan
M. Uchida
Affiliation:
Gifu University Graduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu City, Gifu, Japan
S. Dohi*
Affiliation:
Gifu University Graduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu City, Gifu, Japan
*
Correspondence to: Shuji Dohi, Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. E-mail: shu-dohi@cc.gifu-u.ac.jp; Tel: +81 58 230 6404; Fax: +81 58 230 6405
Get access

Summary

Background and objective

To examine a possible mechanism for the antinociceptive action of the N-methyl-d-aspartate receptor antagonist ifenprodil, we compared its effects with those of ketamine on tetrodotoxin-resistant Na+ channels in rat dorsal root ganglion neurons, which play an important role in the nociceptive pain pathway.

Methods

Experiments were performed on dorsal root ganglion neurons from Sprague–Dawley rats, recordings of whole-cell membrane currents being made using patch-clamp technique.

Results

Both drugs blocked tetrodotoxin-resistant Na+ currents dose dependently, their half-maximal inhibitory concentrations being 145 ± 12.1 μmol (ketamine) and 2.6 ± 0.95 μmol (ifenprodil). Ifenprodil shifted the inactivation curve for tetrodotoxin-resistant Na+ channels in the hyperpolarizing direction and shifted the activation curve in the depolarizing direction. Use-dependent blockade of tetrodotoxin-resistant Na+ channels was more marked with ifenprodil than with ketamine. When paired with lidocaine, these drugs produced similar additive inhibitions of tetrodotoxin-resistant Na+ channel activity.

Conclusions

The observed suppressive effects on tetrodotoxin-resistant Na+ channel activity may, at least in part, underlie the antinociceptive effects of these N-methyl-d-aspartate receptor antagonists.

Keywords

RECEPTORS N-METHYL-d-ASPARTATE, antagonists, ifenprodilKETAMINESODIUM CHANNELS, tetrodotoxin resistantRATANALGESICS, mechanism of action
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 24 , Issue 9 , September 2007 , pp. 782 - 788
Copyright
Copyright © European Society of Anaesthesiology 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Presented in part at the annual meeting of the American Society of Anesthesiologists, Orlando, Florida, 12–16 October 2002.

References

1.Chizh, BA, Headley, PM, Tzschentke, TM. NMDA receptor antagonists as analgesics: focus on the NR2B subtype. T Pharmaco Sci 2001; 22: 636–642.CrossRefGoogle ScholarPubMed
2.Ren, K, Williams, GM, Hylden, JL et al. . The intrathecal administration of excitatory amino acid receptor antagonists selectively attenuated carrageenan-induced behavioral hyperalgesia in rats. Eur J Pharmacol 1992; 219: 235–243.CrossRefGoogle ScholarPubMed
3.Iida, H, Dohi, S, Tanahashi, T et al. . Spinal conduction block by intrathecal ketamine in dogs. Anesth Analg 1997; 85 (1): 106–110.Google ScholarPubMed
4.Bai, L, Zhao, ZQ. Ketamine induced peripheral analgesia in rats. Acta Pharmacol Sinica 1997; 18: 377–379.Google ScholarPubMed
5.Carron, C, Jullien, A, Bucher, B. Synthesis and pharmacological properties of a series of 2-piperidino alkanol derivatives. Arzneimittelforschung 1971; 21 (12): 1992–1998.Google ScholarPubMed
6.Zhi-Shang, Z, Zhi-Qi, Z. Ketamine blockage of both tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels of rat dorsal root ganglion neurons. Brain Res Bull 2000; 52: 427–433.Google Scholar
7.Quasthoff, S, Grosskreutz, J, Schroder, JM et al. . Calcium potentials and tetrodotoxin-resistant sodium potentials in unmyelinated C fibers of biopsied human sural nerve. Neuroscience 1995; 69: 955–965.CrossRefGoogle ScholarPubMed
8.Ogata, N, Tatebayashi, H. Kinetic analysis of two types of Na+ channels in rat dorsal root ganglia. J Physiol (Lond.) 1993; 466: 9–37.CrossRefGoogle ScholarPubMed
9.Oda, A, Ohashi, H, Komori, S et al. . Characteristics of ropivacaine block of Na+ channels in rat dorsal root ganglion neurons. Anesth Analg 2000; 91: 1213–1220.Google ScholarPubMed
10.Song, JH, Huang, CS, Nagata, K et al. . Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther 1997; 282: 707–714.Google ScholarPubMed
11.Akopian, AN, Souslova, V, England, S et al. . The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nature Neurosci 1999; 2: 541–548.CrossRefGoogle Scholar
12.Bean, BP, Cohen, CJ, Tsien, RW. Lidocaine block of cardiac sodium channels. J Gen Physiol 1983; 81: 613–642.CrossRefGoogle ScholarPubMed
13.Sanguinetti, MC, Kass, RS. Voltage-dependent block of calcium channel current in the calf cardiac Purkinje fiber by dihydropyridine calcium channel antagonists. Circ Res 1984; 55: 336–348.CrossRefGoogle ScholarPubMed
14.Kim, YS, Shin, YK, Lee, C, Song, J. Block of sodium currents in rat dorsal root ganglion neurons by diphenhydramine. Brain Res 2000; 881: 190–198.CrossRefGoogle ScholarPubMed
15.Gold, MS, Reichling, DB, Shuster, MJ, Levine, JD. Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors. Proc Natl Acad Sci USA 1996; 93: 1108–1112.CrossRefGoogle ScholarPubMed
16.Brau, ME, Dreimann, M, Olschewski, A et al. . Effect of drugs used for neuropathic pain management on tetrodotoxin-resistant Na+ currents in rat sensory neurons. Anesthesiology 2001; 94: 137–144.CrossRefGoogle ScholarPubMed
17.Catterall, WA. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 2000; 26: 13–25.CrossRefGoogle ScholarPubMed
18.Wildsmith, JA, Brown, DT, Paul, D, Johnson, S. Structure–activity relationships in differential nerve block at high and low frequency stimulation. Br J Anaesth 1989; 63: 444–452.CrossRefGoogle ScholarPubMed
19.Orser, BA, Pennefather, PS, MacDonald, JF. Multiple mechanisms of ketamine blockade of N-methyl-d-aspartate receptors. Anesthesiology 1997; 86: 903–917.CrossRefGoogle ScholarPubMed
20.Avenet, P, Leonardon, J, Besnard, F et al. . Antagonist properties of the stereoisomers of ifenprodil at NR1A/NR2A and NR1A/NR2B subtypes of the NMDA receptor expressed in Xenopus oocytes. Eur J Pharmacol 1996; 296: 209–213.CrossRefGoogle ScholarPubMed
21.Porreca, F, Lai, J, Bian, D et al. . A comparison of the potential role of the tetrodotoxin-insensitive sodium channels, PN3/SNS and NaN/SNS2, in rat models of chronic pain. Proc Natl Acad Sci USA 1999; 96: 7640–7644.CrossRefGoogle ScholarPubMed