Apart from enzyme inducers, valproate (an even enzyme inhibitor) may also negatively affect BMD. However, the untoward effects of AEDs may depend upon their doses and duration of treatment. Although the problem of supplementation of vitamin D and calcium in epileptic patients on AEDs is controversial, there are recommendations to do so.

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By the reaction of 4-methyl-4H-1,2,4-triazole-3-thiol with ethyl bromoacetate, ethyl [(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetate (1) was obtained. This compound was converted to [(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetohydrazide (2). In the reaction of 2 with isothiocyanates, new thiosemicarbazides 3a-3g were obtained. The cyclization of 3a-3g in 2% aqueous solution of sodium hydroxide led to the formation of 4H-1,2,4-triazole-3(2H)-thione derivatives 4a-4g, whereas the cyclization in acid media led to the formation of 2-amino-1,3,4-thiadiazole derivatives 5a-5g. Molecular structure was confirmed by X-ray structure analysis of 3a, 4g, 5a and 5g. Compounds 4a, 4b and 4g were investigated pharmacologically to determine their effect on the central nervous system (CNS) in mice.

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