title: Influence of arachidonyl-2'-chloroethylamide, a selective cannabinoid CB1 receptor agonist, on the anticonvulsant and acute side-effect potentials of clobazam, lacosamide, and pregabalin in the maximal electroshock-induced seizure model and chimney test in mice.
abstract: The influence of arachidonyl-2'-chloroethylamide (ACEA - a selective cannabinoid CB1 receptor agonist) on the anticonvulsant potency and acute adverse-effect potentials of clobazam, lacosamide, and pregabalin was determined in the maximal electroshock-induced seizure model and chimney test in mice. ACEA (2.5 mg/kg, i.p.) significantly enhanced the anticonvulsant potency of pregabalin in the mouse maximal electroshock-induced seizure model by decreasing the median effective dose (ED50 ) of pregabalin from 125.39 to 78.06 mg/kg (P < 0.05). In contrast, ACEA (2.5 mg/kg) had no significant impact on the anticonvulsant potency of clobazam and lacosamide in the mouse maximal electroshock-induced seizure model. On the other hand, ACEA (2.5 mg/kg) did not affect acute adverse effects of clobazam, lacosamide or pregabalin, and the median toxic doses (TD50 ) for the studied anti-epileptic drugs in combination with ACEA did not differ from the TD50 values as determined for the drugs administered alone in the chimney test. In conclusion, ACEA ameliorates the pharmacological profile of pregabalin, when considering both the anticonvulsant and the acute adverse effects of the drug in preclinical study on animals. The combination of pregabalin with ACEA can be of pivotal importance for patients with epilepsy as a potentially advantageous combination if the results from this study translate into clinical settings.
authors.affiliation: Department of Public Health, Institute of Rural Health, Jaczewskiego 2, PL 20-950, Lublin, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florek-Luszczki
authors.affiliation: Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, PL 20-950, Lublin, Poland.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Zagaja
authors.affiliation: Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, PL 20-950, Lublin, Poland.|Department of Pathophysiology, Medical University, Ceramiczna 1, PL 20-150, Lublin, Poland.
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Luszczki
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use*; D001095:Arachidonic Acids / Q000494:pharmacology*; D001259:Ataxia / Q000139:chemically induced / Q000517:prevention & control; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000078306:Clobazam; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004597:Electroshock; D000078334:Lacosamide; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D000069583:Pregabalin / Q000009:adverse effects / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D001095:Arachidonic Acids; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; D001569:Benzodiazepines; D000078306:Clobazam; D000069583:Pregabalin; D000078334:Lacosamide
keywords: anti-epileptic drugs; arachidonyl-2′-chloroethylamide; cannabinoids; chimney test; maximal electroshock seizure test; protective index