Anticonvulsant Activity of Novel Benzimidazole Derivatives
979
Table VI. Anticonvulsant screening of some novel benzimidazole derivatives on tonic seizures induced by pentyl-
enetetrazole in male rats
PTZ Seizure Test
S. No. Treatment Group Dose (mg/kg)
Onset Time (sec)a Duration of HLTE (sec)a % Inhibition of Convulsions
1
2
3
4
5
6
Control
Standard
1A
-
48.17 ± 0.30b
34.33 ± 0.33b
−
30
30
30
30
30
0
0
10000.
064.64
027.97
017.13
051.06
b
b
73.00 ± 0.36
62.83 ± 0.40
52.83 ± 0.30
12.83 ± 0.30
16.17 ± 0.40
28.50 ± 0.56
b
b
1B
1C
1D
b
b
b
b
59.50 ± 0.42
23.67 ± 0.49
a
b
Values represent means ± S.E.M. (n = 6).
Values are significantly different at < 0.0001 vs control rats by One way ANOVA followed by Dunnett's Multiple Com-
parison Test.
p
GABA/BZd binding affinity among all the compounds.
QSAR studies of this series suggest the possibility of
Analysis by Examples. Wiley VCH, New York, USA,
2000).
(
bioisosteric replacement of benzotriazine with a benzi- Chen, J., Sun, X. Y., Chai, K. Y., Lee, J. S., Song, M. S., and
midazole ring possessing a different lipophilic substi-
tution on it. Two other descriptors i.e., charge-dipole
and dipole-dipole energy, says about their role in de-
signing new models with potent anticonvulsant activity.
These findings prompted us to undertake synthesis of
new derivatives possessing benzimidazole as the phar-
macophore. All Nitro-benzimidazole are active against
tonic convulsions induced by electrical and chemical
stimuli in mice. Among them, 1A and 1B show pro-
mising activity against the MES and PTZ-induced
convulsions. Preliminary data suggests that this class
of compounds only partially exerts their anticonvulsant
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ACKNOWLEDGEMENTS
Guerrini, G., Ciciani, G., Cambi, G., Bruni, F., Selleri, S.,
Melani, F., Montali, M., Martini, C., Ghelardini, C., Norcini,
M., and Costanzoa, A., Novel 3-aroylpyrazolo [5,1-c][1,2,4]
benzotriazine 5-oxides 8-substituted, ligands at GABAA/
benzodiazepine receptor complex: Synthesis, pharmacolo-
gical and molecular modeling studies. Bioorg. Med. Chem.,
The authors are thankful to IIT, Mumbai and
Dhanwantri research & analytical laboratory, Kim,
Gujarat for spectral analysis of all new compounds.
16, 4471-4489 (2008).
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