Evaluation of isonicotinoyl-.GAMMA.-aminobutyric acid (GABA) and nicotinoyl-GABA as pro-drugs of GABA.

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Abstract
Isonicotinoyl-.gamma.-aminobutyric acid (GABA) (IG) and nicotinoyl-GABA (NG), candidate prodrugs of GABA, were assessed by measuring various pharmacological responses such as anticonvulsant effect, prolongation of pentobarbital sleeping time and depressive effect on rearing or ambulation in general behavior, in relation to the GABA level in the mouse brain. The GABA level after the i.p. administration of IG at a dose of 1000 mg/kg increased significantly from 2.30 .+-. 0.02 .mu.mol/g wet wt in the control to 2.93 .+-. 0.05 .mu.mol/g wet wt, while NG caused only a slight increase in GABA level. IG showed a stronger anticonvulsant effect, greater prolongation of pentobarbital sleeping time and greater depressive effect on rearing in general behavior than NG did. The pharmacological effect of IG or NG corresponded well to the GABA level in the brain.