Title:Synthesis and Evaluation of Novel Diazaspiro Hydantoins as Potential Anticonvulsants
Volume: 17
Issue: 3
Author(s): Channapillekoppal S.A. Kumar*, Bantal Veeresh, Kanikahalli C. Ramesha, Channapillekoppal S.A. Raj, Kanikahalli M. Mahadevaiah and Salekoppal B.B. Prasad
Affiliation:
- Centre for Materials Science, Vijnana Bhavan, Manasagangotri, University of Mysore, Mysore-570 006,India
Keywords:
Anticonvulsant, diazaspiro hydantoins, hydantoins, maximal electroshock, phenytoin, toxicity.
Abstract: Background: Epilepsy, one of the most frequent neurological afflictions in man characterized
by excessive temporary neuronal discharges resulting in uncontrolled convulsion, requires special
medical attention. Though several new anticonvulsants are introduced, some types of seizures are still
not adequately treated with current therapy. Toxicity, intolerance, and lack of efficacy for certain
types of seizure are some of the limitations of the current medications.
Methods: Maximal electroshock (MES) seizure model was used in the present study to evaluate the
anticonvulsant activity of the drugs. Seizures were induced in ten weeks old male Wistar rats (200-220
g) by delivering electro shock of 150 mA for 0.2 sec by means of a convulsiometer through a pair of
ear clip electrodes. The test compounds (1-10, 100 mg/kg) were administered by oral route 30 mins
before the maximal electroshock seizure test by suspending in carboxymethylcellulose (1%). The
animals were observed closely for 2 mins. The percentage of inhibition of seizure relative to control
was recorded and calculated. Phenytoin (100 mg/kg, p.o) was used as a standard drug. The data was
analysed by using one way ANOVA followed by dunnett's test.
Results: In our present series of compounds the active compounds possess all the requirements essential
for anticonvulsant activity as proposed by Dimmock and others. In this study, it reveals that, compounds
showing anticonvulsant activity with more lipophilic N-substitution group are more active than
hydrophobic substitution in the hydantoin ring. The rapid onset of action is believed to be due to the
substitution of more lipophilic propyl group in the N-substitution in the hydantoin moiety. Evidently,
this distal hydrophobic centre alters the bioavailability of the molecules.
Conclusion: The results are encouraging and show that, the hydantoins are more potential molecules
for the treatment of anticonvulsant. Anticonvulsants have greatly improved the lives of people with
epilepsy. Approximately 70% of patients can achieve complete freedom from seizures with appropriate
treatment. Lipophilicity appears to govern the MES activity. If there is lipophilic moiety, then
MES activity is favoured. All the compounds have shown promising and significant protective effect
on maximal electroshock induced seizures when compared to vehicle treated control rats.
