Research Article The Anticonvulsant Enaminone E139 Attenuates

Copyright © 2013 Dhandapani Thangamani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The enaminone methyl 4-(4-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139) has anticonvulsant activities. It has been reported to have a better safety profile than some anticonvulsant drugs. Since some anticonvulsant drugs are used in the management of neuropathic pain, we evaluated the effects of E139 in rodent models of acute pain and paclitaxel-induced neuropathic pain. The reaction latency to thermal stimuli (hot-plate test) of BALB/c mice was recorded before and after intraperitoneal treatment with paclitaxel (2mg/kg, i.p. for 5 consecutive days), and after treatment with E139 (0.1–40mg/kg), amitriptyline (10mg/kg), and gabapentin (10 and 30mg/kg). Mechanical allodynia in paclitaxel-treated Sprague Dawley (SD) rats was measured using a dynamic plantar aesthesiometer before and after treatment with E139 (10 and 20mg/kg) or its vehicle for four consecutive days from day 7 after first administration of paclitaxel (16mg/kg on two alternate days). Administration of E139 (10–40mg/kg) produced antinociceptive activity against thermal nociception in näıve mice. Treatment with E139, amitriptyline, or gabapentin reduced paclitaxel-induced thermal hyperalgesia. E139 reduced paclitaxel-induced mechanical allodynia, with the effects lasting longer (24 h) after repetitive dosing. Our results indicate that E139 has antinociceptive activity and attenuates paclitaxel-induced neuropathic pain in rodents. 1