[Antinociceptive effects of the enantiomorphs and its main metabolite in streptozotocin-induced diabetic mice].
The antinociceptive effects of the enantiomorphs of mexiletine (2-(2, 6-dimethylphenoxy)-1-methylethylamine monohydrochloride) and its main metabolite ((+/-)2-(2-hydroxymethyl-6-methylphenoxy)-1-methylethylamine oxalate: KOE2259) were studied in streptozotocin-induced diabetic mice using the tail-pinch and tail-flick test. Both (+)mexiletine and (-)mexiletine, at doses of 10 and 30 mg given i.p., produced dose-dependent inhibition of the tail-pinch response in diabetic, but not non-diabetic mice. On the other hand, KOE2259 had no significant effect on the tail-pinch response in both non-diabetic and diabetic mice. (+/-) Mexiletine given po also produced marked inhibition of the tail-pinch and tail-flick responses in both non-diabetic and diabetic mice. However, lidocaine, given either i.p. or po, had no significant effect on the tail-pinch response in both non-diabetic and diabetic mice. Intraperitoneal administration of mexiletine (30 mg/kg) significantly increased the serum beta-endorphin level in diabetic mice, but not in non-diabetic mice. These results indicate that both enantiomorphs of mexiletine produced an antinociceptive effect in diabetic mice. Furthermore, it is possible that the activation of the endogenous beta-endorphinergic system may be, at least in part, involved in the antinociceptive effect of mexiletine.
Kamei
J
J
Department Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003929:Diabetic Neuropathies / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008801:Mexiletine / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008813:Mice, Inbred ICR; D013237:Stereoisomerism; D013311:Streptozocin; D001615:beta-Endorphin / Q000097:blood
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D013311:Streptozocin; D001615:beta-Endorphin