Potentiation of valproate-induced anticonvulsant response by nigella sativa seed constituents: the role of GABA receptors

This study investigated antiepileptic effects of the main constituents of Nigella sativa [NS] seed [i.e. aqueous extract [AE], fixed oil [FO], volatile oil [VO]] and the main components of its VO [i.e. thymoquinone, alpha-pinene and p-cymene] using pentylenetetrazole [PTZ] and maximal electroshock [MES]-induced convulsions. The potential of these constituents to induce minimal neurological deficit [MND] was also evaluated by using chimney test. Except for the FO, all of the NS seed constituents protected mice effectively against PTZ-induced convulsions. The activity of the VO in this model maybe attributed mainly to its content of thymoquinone and p-cymene and to a lesser extent, alpha-pinene. VO and its component p-cymene effectively suppressed convulsions induced by MES. The contents of p-cymene present in the effective dose of the VO maybe partially responsible for its anti-seizure effects. All of the NS seed constituents induced varying degrees of MND in the chimney test. MND induced by VO may pertain to its contents of thymoquinone [63%], p-cymene [23%] and alpha-pinene [<14%]. Protective indices of p-cymene and thymoquinone were closer to one, but only in PTZ model. Exploration on the role of receptors suggests that picrotoxin and bicuculline-sensitive GABA receptors, most probably GABAA receptors, mediate an increase in GABAergic response. In the part dealing with the interaction of valproate with thymoquinone, it can be mentioned that thymoquinone increased the potency of valproate in both PTZ and MES models

Synthesis of a new series of substituted pyrimidines and its evaluation for antibacterial and antinociceptive effects

Pyrimidines are a well known group of compounds reported to have different biological activities. Prompted from the diversity of its wider use and being an integral part of genetic material, an effort was made to synthesize a novel series of amino-pyrimidine derivatives of pharmaceutical interest by condensing the guanidinyl derivative of nalidixic acid with different chalcones. The structures of all synthesized compounds were established on the basis of IR and 1HNMR spectral studies. All of the new compounds in this series were screened for antimicrobial activity. Gram-ve and Gram-ye strains were used to ascertain the spectrum of activity. ED5O values in the tail flick test were determined and recorded. Analgesic potential of compounds by using tail flick test in SWR male mice have also revealed promising results. All of the derivatives were effective in Gram-ve test against E. coli. None of the compounds show any inhibition of Gram+ve strain S. aureus. m-Bromo substitution derivative of amino-pyrimidines showed appreciable activity against E. coli, while 2, 4 dichloro and p-chloro substitution derivatives also demonstrated improved activity. Compound 4 was most potent. The order of potency for these derivatives was 4>5 >/= 6>1>2>7>3. Parallel to antimicrobial activity, m-bromo substitution derivative showed significant [P<0.01] antinociceptive response in comparison to control, and this effect was comparable to aspirin group. Trimethoxy substitution of benzene ring demonstrated moderate activity, whereas p-bromo substitution essentially had no antinociceptive effects in mice. Comparing meta-and para-bromo substitutions, there had been significant [P<0.01] difference in the antinociceptive response of both the bromo-substituted derivatives. It was observed that bromo-substitution at meta-position demonstrated comparatively higher potential for its antibacterial as well as antinociceptive properties