Lack of stereoselectivity for the antiallodynic effect of mexiletine in spinally injured rats.
Systemically administered mexiletine, an antiarrhythmic, has been shown to also possess analgesic properties in some conditions of neuropathic pain. It has been suggested that the analgesic effect of mexiletine may be derived from the action of one of its optical isomers, (+)(S)-mexiletine. In the present study, we have compared the effects of systemic (-)-(R)- and (+)-(S)-mexiletine, on chronic mechanical allodynia-like behaviour in spinally injured rats, a model of central neuropathic pain in which racemic mexiletine has been shown to be active. I.p. racemic mexiletine as well as (-)-(R)- and (+)(S)-mexiletine at 25 mg/kg all produced significant, but brief, alleviation of mechanical allodynia in a similar fashion as assessed with von-Frey hair elicited vocalization in the spinally injured rats. A slight increase in motor impairment was observed in all three groups which reached statistical significance for the racemic mexiletine and (+)-(S)-mexiletine. Our results suggest that both isomers of mexiletine contribute to the antiallodynic effect in this model of central pain.
Wu
W P
WP
Department of Medical Laboratory Sciences and Technology, Division of Clinical Neurophysiology, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden.
Nordmark
J
J
Wiesenfeld-Hallin
Z
Z
Xu
X J
XJ
D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D008801:Mexiletine / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*; D013237:Stereoisomerism; D014828:Vocalization, Animal / Q000187:drug effects
D000700:Analgesics; D008801:Mexiletine