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cages and allowed free access to food and water. The title
compounds (1-14) were suspended in 0.5% methyl cellu-
lose/water mixture or in polyethylene glycol (PEG 200).
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3.2.1. Anticonvulsant Screening
The anticonvulsant evaluations were undertaken by the
Anticonvulsant Screening Program, National Institute of
Neurological Disorders and Stroke (NINDS), National Insti-
tute of Health, using their reported procedures [19, 20]. Ini-
tially all compounds were administered intraperitoneally in
doses of 30, 100 and 300mg/kg to one to four mice. Activity
was established using MES and scPTZ tests.
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[8]
[9]
One of the compounds (4) was also examined for MES
ED50, MES TD50, scPTZ ED50 and scPTZ TD50 studies.
3.2.2. Neurotoxicity Screening
The rotorod test was used to evaluate neurotoxicity. The
animal was placed on a 3.2 cm diameter knurled rod rotating
at 10 rpm. Normal mice can remain on a rod rotating at this
speed indefinitely. Neurological toxicity is defined as the
failures of the animal to remain on the rod for 1.0min.
Trained animals were given intraperitoneal injections of the
test compounds in doses of 30, 100 and 300mg/kg. Neuro-
toxicity was indicated by the inability of the animal to main-
tain equilibrium on the rod for at least 1.0 min in each of
three trials. Results are expressed as number of animals ex-
hibiting toxicity/ number of animals tested [21].
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3.2.3. Isolation of Rat Brain Regions and GABA Assay
The GABA assay for compounds 4 and 12 was per-
formed in brain tissue extracts enzymatically as described in
the literature [22]. Adult Wistar rats were used for this pur-
pose. After 2.0 hrs of drug administration intraperitoneally,
the animal was sacrificed by decapitation and the brain re-
gions, midbrain, olfactory lobe, cerebellum and medulla ob-
longata were dropped into separate vials containing 4-6ml of
ice cold 80% ethanol and processed further as described in
the literature [23].
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Jain, J. S.; Srivastava, R. S.; Aggrawal, N.; Sinha, R. Synthesis and
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200-204.
Mishra, V.; Pandeya, S. N. Analgesic activity and hypnosis poten-
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zone derivatives. Acta. Pharm., 2001, 51, 83-88.
Mishra, V.; Pandeya, S. N.; Pannecouque, C.; Witvrouw, M.; De
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ACKNOWLEDGEMENTS
The authors are thankful to the Director, Department of
Pharmaceutical Sciences, Meerut Institute of Engineering
and Technology, Meerut, Uttar Pradesh, India for providing
the infrastructure for undertaking the project. One of the
authors James Stables deeply acknowledges NINDS, NIH,
Bethesda, MD, USA for undertaking the pharmacological
screening of synthesized compounds. Authors are also thank-
[19]
[20]
[21]
1
ful to Mr. M.N. Lal, IIT, Delhi, for the generation of H
NMR data.
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Received: August 27, 2009
Revised: December 23, 2009
Accepted: December 23, 2009