The synthesis of new pyrazine substituted 1,3,4-thiadiazole derivatives was carried out in good yield by the reaction of pyrazine substituted 1,3,4-thiadiazoles with various sulfonyl chlorides. A chemical structure of all the new compounds was confirmed by 1H NMR and mass spectral data. The new compounds were screened for their anticonvulsant activity against maximal electroshock (MES) seizure method. Rotarod method was employed to determine the neurotoxicity. Few compounds showed significant changes in anticonvulsant activity. The same compounds showed no neurotoxicity at the maximum dose administered (100？mg/kg). 1. Introduction Epilepsy has been recognized as a neurological disorder, affecting a large section of people across the world. The word epilepsy usually describes a group of common chronic neurological disorders characterized by recurrent unprovoked seizures due to excessive neuronal firing or synchronous neuronal activity in the brain [1, 2]. Seizures may vary from the briefest lapses of attention or muscle jerks to severe and prolonged convulsions [3]. The maximal electroshock (MES) test is a predictor of compounds that are active against seizures [4]. The anticonvulsant drug design is based on the presumption that at least one phenyl or similar aromatic group in close proximity to two electron donor atoms in the compound is required for the activity in MES [5, 6]. Newer drugs such as flupirtine [7], topiramate [8], zonisamide [9], and vigabatrin [10] have emerged as promising anticonvulsants. Pyrazines and its derivatives play an important role in the drug discovery realm. In particular the structural analogue of purines derivatives presents various pharmacological activities such as antibacterial [11], anti-inflammatory [12], antidepressant [13], and antiproliferative activities [14]. Thiadiazoles exhibit a broad spectrum of biological effectiveness such as antiparkinsonism [11], antihistaminic [15], and antiasthmatic [16]. Thiazolidin-4-one derivatives are also known to exhibit diverse bioactivities such as anticonvulsant [17], antidiarrheal [18], antihistaminic [19], antidiabetic [20], cardioprotective [21], and anticancer [22]. Similarly, 2,5-disubstituted 1,3,4-thiadiazoles also display wide spectrum of activities such as antibacterial [23] and anticonvulsant [24]. In the present study, a series of new pyrazine substituted 1,3,4-thiadiazole derivatives 7(a–o) have been synthesized and their anticonvulsant effects are determined through maximal electroshock (MES) seizure test. 2. Materials and Methods 2.1. Chemistry Melting range was
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