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Attenuating Effect of Mexiletine Hydrochloride on Herpetic Pain in Mice Infected With Herpes Simplex Virus

Attenuating Effect of Mexiletine Hydrochloride on Herpetic Pain in Mice Infected With Herpes Simplex Virus

Kazuhito Asano, Tatsuo Sameshima, Hiroshi Shirasawa, Tadashi Hisamitsu

J Pharm Pharmacol. 2003 Oct;55(10):1365-70.

PMID: 14607018

Abstract:

The influence of mexiletine hydrochloride on herpes-related pain responses was examined using mice infected with herpes virus. BALB/c mice were inoculated with herpes simplex virus (HSV; 1 x 10(6) plaque-forming units) on the right hind paw, and the contralateral hind paw was without inoculation. The changes in nociceptive threshold were examined using electric von fray meter. BALB/c mice inoculated with HSV showed a decrease in nociceptive threshold. Intraperitoneal administration of mexiletine prevented the decrease in nociceptive threshold dose-dependently in HSV-inoculated mice, which was firstly observed at a dose of 15.0 mg kg(-1), and peaked at doses more than 17.5 mg kg(-1). This antinociceptive effect of mexiletine attained peaks at 60-90 min after administration and declined gradually to non-treated levels by 150 min. Intraperitoneal administration of mexiletine at a dose of 17.5 mg kg(-1) (but not 10.0 mg kg(-1)) caused significant increase in beta-endorphin levels in the mid brain and hypothalamus of HSV-inoculated mice. However, mexiletine scarcely affected noradrenaline (norepinephrine) levels in the pons and medulla oblongata, even when HSV-inoculated mice were treated with 17.5 mg kg(-1) mexiletine. These results strongly suggested that mexiletine exerts antinociceptive effects on herpes-related pain through enhancement of beta-endorphin levels in the central nervous system in HSV-inoculated mice. It is also suggested that mexiletine will be a good candidate for an antinociceptive drug in the treatment of acute herpetic pain in man.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP5370014-A	Mexiletine hydrochloride		5370-01-4	Price

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