Protective action of nicotinic acid benzylamide in a variety of chemically-induced seizures in mice

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• 作者：Mariusz J. Świąder^a ; ^{mariusz.swiader@am.lublin.pl" class="auth_mail" title="E-mail the corresponding author} ; Jarogniew J. Łuszczki^b ; ^c ; Ryszard Paruszewski^d ; Katarzyna Świąder^e ; Waldemar A. Turski^a
• 关键词：AMPA ; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ; BIC ; bicuculline ; ED50 ; median effective dose ; KA ; kainic acid ; Nic-BZA ; nicotinic acid benzylamide ; NMDA ; N-methyl-d-aspartic acid ; PI ; protective index ; PILO ; pilocarpine ; PTZ ; pentylenetetrazole ; TD50 ; median toxic dose
• 刊名：Pharmacological Reports
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：68
• 期：2
• 页码：297-300
• 全文大小：248 K

文摘

The study aims to assess the anticonvulsant effects offered by benzylamide nicotinic acid (Nic-BZA) in many animal models of chemically-induced seizures (i.e., pentylenetetrazole [PTZ], pilocarpine [PILO], bicuculline [BIC], α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], kainic acid [KA], and N-methyl-d-aspartic acid [NMDA]). Additionally, it analyses side effects of administering Nic-BZA in the form of loss of co-ordination and memory impairment as evaluated in the rotarod and passive avoidance tests, respectively.

Results

Antiseizure activity of Nic-BZA was reported in numerous models of chemically-induced seizures and its ED₅₀ value was 37.1 mg/kg for PTZ, 53.0 mg/kg for AMPA, 81.4 mg/kg for BIC, 86.3 mg/kg for KA, and 182.6 mg/kg for PILO. Moreover, Nic-BZA was totally ineffective (in dosages of up to 200 mg/kg) in mice challenged with NMDA-induced seizures. The evaluation of the side effects present shortly after dosing in the rotarod test has revealed neurotoxicity of Nic-BZA with experimentally determined TD₅₀ value of 188.5 mg/kg. Protective index (PI) assessment analysis for Nic-BZA has disclosed a substantial difference between the dosage resulting in acute impairment of co-ordination and the dosage resulting in anticonvulsant effect in various chemically evoked seizures, remaining practically ineffective (in dosages of up to 200 mg/kg) in mice subjected to the NMDA-induced seizure test. Additionally, Nic-BZA (in dosages of up to 100 mg/kg) did not impair long-term memory in mice.

Conclusions

Summing up, Nic-BZA has a wide anticonvulsant effect in different experimental epilepsy models.