L-Type Calcium Channel Mediates Anticonvulsant Effect of Cannabinoids in Acute and Chronic Murine Models of Seizure |
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Authors: | Nima Naderi Leila Ahmad-Molaei Ali Mazar-Atabaki Abdolaziz Ronaghi Zahra Shirazi-zand Seyed Mehrdad Motiei-Langroudi Somayeh Eslahkar |
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Institution: | (1) Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, No. 2660, Vali-e-Asr Ave., P.O. Box: 14155-6153, 1996835113 Tehran, Iran;(2) Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;(3) Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran;(4) Department of Physiology, Faculty of Medicine, Shahed University of Medical Sciences, Tehran, Iran |
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Abstract: | The anticonvulsant activities of cannabinoid compounds have been shown in various models of seizure and epilepsy. At least,
part of antiseizure effects of cannabinoid compounds is mediated through calcium (Ca2+) channels. The L-type Ca2+ channels have been shown to be important in various epilepsy models. However, there is no data regarding the role of L-type
Ca2+ channels in protective action of cannabinoids on acute and chronic models of seizure. In this study, the effects of cannabinoid
compounds and L-type Ca2+ channels blockers, either alone or in combination were investigated using acute model of pentylenetetrazole (PTZ)-induced
seizure in mice and chronic model electrical kindling of amygdala in rats. Pretreatment of mice with both cannabinoid CB1
receptor agonist arachidonyl-2′-chloroethylamide (ACEA) and endocannabinoid degradating enzyme inhibitor cyclohexylcarbamic
acid 3′-carbamoyl-biphenyl-3-yl ester (URB597) produced a protective effect against PTZ-induced seizure. Administration of
various doses of the two L-type Ca2+ channel blockers verapamil and diltiazem did not alter PTZ-induced seizure threshold. However, co-administration of verapamil
and either ACEA or URB597 attenuated the protective effect of cannabinoid compounds against PTZ-induced seizure. Also, pretreatment
of mice with diltiazem blocked the anticonvulsant activity of both ACEA and URB597. Moreover, (R)-(+)-2,3-dihydro-5-methyl-3(4-morpholinyl)methyl]pyrrolo1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate
(WIN55,212-2), the non-selective cannabinoid CB1 and CB2 receptor agonist showed anticonvulsant effect in amygdala-kindled
rats. However, co-administration of WIN55,212-2 and verapamil attenuated the protective properties of WIN55,212-2. Our results
showed that the anticonvulsant activity of cannabinoid compounds is mediated, at least in part, by L-type Ca2+ channels in these two models of convulsion and epilepsy. |
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