Anna Chodkowska

Effects of calcium channel inhibitors upon the efficacy of common antiepileptic drugs.

Diltiazem and nifedipine (both 1.25 mg/kg) markedly potentiated the protective action of carbamazepine and diphenylhydantoin against maximal electroshock-induced seizures in mice. These calcium channel inhibitors retained their activity at lower doses. Diltiazem and nifedipine (2.5 mg/kg) also moderately potentiated the efficacy of phenobarbital and valproate. Verapamil (up to 10 mg/kg) was not effective against the action carbamazepine, diphenylhydantoin, phenobarbital, and valproate. None of the calcium channel inhibitors used (up to 40 mg/kg) influenced aminophylline-induced convulsions and mortality. Moreover, the anti-aminophylline activity of valproate and phenobarbital was not potentiated by the calcium channel inhibitors in doses up to 10 mg/kg. Further, combination of carbamazepine, ethosuximide, and trimethadione with the calcium channel inhibitors (up to 10 mg/kg) did not offer any protection against aminophylline-induced convulsions. It can be concluded that calcium channel inhibitors enhance the protective efficacy of some antiepileptics against electroconvulsions. A pharmacokinetic interaction does not seem to be responsible for this effect.

Synthesis and pharmacological properties of 3-(2-methyl-furan-3-yl)-4-substituted-Δ2-1,2,4-triazoline-5-thiones

By the reaction of 2-methyl-furan-3-carboxylic acid hydrazide with isothiocyanates, 1-[(2-methyl-furan-3-yl)carbonyl]-4-substituted thiosemicarbazides 1 were obtained. Further cyclization with 2% NaOH led to the formation of 3-(2-methyl-furan-3-yl)-4-substituted-Δ2-1,2,4-triazoline-5-thiones 2. The pharmacological effects of 2 on the central nervous system in mice were investigated. Strong antinociceptive properties of the investigated derivatives were observed in a wide range of doses.

Synthesis and biological activity of O-acyl and O-alkyl chelidonine derivatives

A group of 11 derivatives of chelidonine was obtained by acylations and/or alkylations of the secondary hydroxyl group with the aim of testing their biological activity. This paper focuses on the new derivatives influence on CNS in mice. The highest activity was observed for compounds 2c, 3c and 4, which produced antinociceptive and antiserotoninergic effects, not recorded for the parent alkaloid 1.

Chemical and Pharmacological Properties of 3-(Thiophen-2-yl)-4-substituted-Δ 2-1,2,4-triazoline-5-thiones

Three 3-(thiophen-2-yl)-4-substituted-Δ 2 -1,2,4-triazoline-5-thiones were synthesized by intramolecular cyclization of 1-(thiophen-2-ylcarbonyl)-4-substituted thiosemicarbazides in alkaline medium. Their effects on the central nervous system (CNS) of mice in some behavioral tests were investigated. All investigated compounds displayed antinociceptive activity. The correlation between the structural features and bioactivity has been discussed.

Determination of Lipophilicity of Allyl Thiosemicarbazide, N1-Thiocarbamylamidrazone Derivatives, and their Cyclic Products by RP-HPLC, RP-TLC, and Theoretical Methods: Effects of Selected Compounds on the CNS of Mice

The allyl thiosemicarbazide, N1-thiocarbamylamidrazone derivatives, and the products of their cyclization: the 1,2,4-triazole, 1,3,4-thiadiazole, 1,2,4-triazole[3,4-b]1,3-thiazine, 1,2,4-triazole[3,2-b]1,3-thiazine, 1,3,4-thiadiazole[3,2-a]pyrimidine, 5,6-dihydrothiazolo[2,3-c][1,2,4]triazole, and benzoic acid derivatives have been analyzed by RP-HPLC and RP-TLC methods using the methanol-water mixtures as the mobile phase and the octadecyl stationary phase. The lipophilicity was expressed as the chromatographically derived descriptors: mean of k (mk), mean of logk (mlogk), logkW, S, and ϕ0, scores of k, logk, and RM corresponding to the first principal component. Additionally, the authors propose to introduce a descriptor (logkm) corresponding to the residual specific interactions. Chromatographic parameters of lipophilicity were compared with the partition coefficient (logP) calculated by various softwares (milogP, clogP, AlogPs, AClogP, AlogP, MlogP, KOWWIN, XlogP2, XlogP3). The matrices were created with logkW or RMW and logP and they have been the subject of PCA analysis. The effects of the selected compounds on the central nervous system (CNS) of mice were studied.

Pharmacological Study on Some New 3-((1-Methylpyrrol-2-yl)- methyl)-4-Substituted 4,5-Dihydro-1H-1,2,4-triazol-5-ones

3-[(1-Methylpyrrol-2-yl)methyl]-4-substituted 4,5-dihydro-1H-1,2,4-triazol-5-ones were obtained by the cyclization reaction of 1-[(1-methylpyrrol-2-yl)acetyl]-4-substituted semicarbazides in alkaline medium. The effects of the synthesized compounds of the central nervous system of mice were studied