Anticonvulsant Effectiveness and Neurotoxicity Profile of 4-butyl-5-[(4-chloro-2-methylphenoxy)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) in Mice

被引：4

作者：

Drabik, Magdalena ^{[1
]}

Gluszak, Mariusz ^{[1
]}

Wroblewska-Luczka, Paula ^{[1
]}

Plewa, Zbigniew ^{[2
]}

Jankiewicz, Marek ^{[3
]}

Kozinska, Justyna ^{[4
]}

Florek-Luszczki, Magdalena ^{[5
]}

Plech, Tomasz ^{[6
]}

Luszczki, Jarogniew J. ^{[1
,7
]}

机构：

[1] Med Univ Lublin, Dept Pathophysiol, Jaczewskiego 8b, PL-20090 Lublin, Poland

[2] 1 Mil Clin Hosp Outpatient Clin Lublin, Dept Gen Oncol & Minimally Invas Surg, Lublin, Poland

[3] Med Univ Lublin, Dept & Clin Cardiol, Lublin, Poland

[4] Med Univ Lublin, Dept & Clin Hematolooncol & Bone Marrow Transplan, Lublin, Poland

[5] Inst Rural Hlth, Dept Med Anthropol, Lublin, Poland

[6] Med Univ Lublin, Dept Pharmacol, Lublin, Poland

[7] Inst Rural Hlth, Isobolog Anal Lab, Lublin, Poland

来源：

NEUROCHEMICAL RESEARCH | 2021年 / 46卷 / 02期

关键词：

Antiepileptic drugs; Tonic-clonic seizures; Pharmacokinetic; pharmacodynamic interaction; Protective index; 1; 2; 4-triazole-3-thione; ANTIEPILEPTIC DRUGS; SCREENING-PROGRAM; NEUROLOGICAL DISORDERS; NATIONAL INSTITUTE; EPILEPSY; SEIZURES; ACID; OXCARBAZEPINE; MECHANISMS; VALPROATE;

D O I：

10.1007/s11064-020-03175-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protective (antiseizure) effects of 4-butyl-5-[(4-chloro-2-methylphenoxy)-methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) and acute neurotoxic effects were determined in the tonic-clonic seizure model and rotarod test in mice. The interaction profile of four classic antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) with TPL-16 was also determined in the tonic-clonic seizure model in mice. The protective effects of TPL-16 from tonic-clonic seizures (as ED50 values) and acute neurotoxic effects of TPL-16 (as TD50 values) were determined in 4 pretreatment times (15, 30, 60 and 120 min after its i.p. administration), in adult male albino Swiss mice. The interaction profile of TPL-16 with carbamazepine, phenobarbital, phenytoin and valproate in the tonic-clonic seizure model was determined with isobolographic analysis. Total concentrations of carbamazepine, phenobarbital, phenytoin and valproate were measured in the mouse brain homogenates. The candidate for novel antiepileptic drug (TPL-16) administered separately 15 min before experiments, has a beneficial profile with protective index (as ratio of TD50 and ED50 values) amounting to 5.58. The combination of TPL-16 with valproate produced synergistic interaction in the tonic-clonic seizure model in mice. The combinations of TPL-16 with carbamazepine, phenobarbital and phenytoin produced additive interaction in terms of protection from tonic-clonic seizures in mice. None of the total brain concentrations of classic AEDs were changed significantly after TPL-16 administration in mice. Synergistic interaction for TPL-16 with valproate and the additive interaction for TPL-16 with carbamazepine, phenobarbital and phenytoin in the tonic-clonic seizures in mice allows for recommending TPL-16 as the promising drug for further experimental and clinical testing.

引用

页码：396 / 410

页数：15

共 22 条

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