CNS Disorders: Treatment Approach with Novel Derivatives of Coumarins in Experimental Albino Mice

Aim: The present study was aimed to assess the treatment of CNS disorders of the novel coumarin (Benzopyran-2-one) derivatives i.e., 2- (4-isobutylphenyl) -N- (4-methyl-2-oxo-2H-chromen-7-yl) propanamide (comp-I), 2-(2-(2,6- dichlorophenylamino) phenyl) –N- (4- methyl-2-oxo-2H-chromen-7-yl) acetamide (comp-II) and 2-(1-(4-chlorobenzoyl)-6-methoxy-2-methyl-1H-indol-3-yl)-N-(4-methyl-2-oxo-2H-chromen-7-yl) acetamide (comp-III) by using the various pharmacological activities i.e., anti-convulsant, anxiolytic, spontaneous motor activity, skeletal muscle relaxant and analgesic activities along with assay of serum gamma amino butyric acid (GABA) levels. Methods: Investigation of all CNS Disorders were evaluated by performing the various pharmacological activities using the different screening models i.e., anti-convulsant activity by pentylenetetrazole (PTZ) induced seizure model, anxiolytic activity (exploratory behaviour) by evasion test, assay of GABA levels after anti-convulsant model was performed by using chromatographic technique, spontaneous motor activity (SMA) by actophotometer test, skeletal muscle relaxation by rotarod test and analgesic activity by Eddy’s hot plate and Haffner’s tail clip methods in Wistar albino mice.

Results: All the Coumarin derivatives showed significant anti-convulsant activity by prolonging the onset of seizures and reducing the duration of seizures and mortality rate when compared with control group. The test compounds showed significant anxiolytic effect. The serum GABA levels were significantly elevated in the treated groups, when compared with that of control group. The test compounds showed significant decrease in the spontaneous motor activity. The test compounds significantly showed a skeletal muscle relaxation after 30 min of dosing. The test compounds showed significant increase in paw licking time to heat stimuli in hot plate method and increase in the reaction time of mice to dislodge the clip. Conclusion: The present study has revealed that all the Benzopyran-2-one derivatives possess significant neuropharmacological properties confirmed by anti-convulsant, anxiolytic, skeletal muscle relaxant, analgesic effects and decrease in spontaneous motor activity at a dose of 20 mg/kg p.o. in swiss albino mice.