A 1,2-benzisoxazole derivative represented by general formula (I) and a salt thereof, said compound (I) being excellent in the protection against cerebral hypoxia, having the macrobiotic effect on the animals suffering from cerebral ischemia and an antispasmodic effect, having reduced effect on the central nervous system, and having a high safety, thus being useful for treating not only the acute stage of cerebral circulation disorder but also the chronic stage thereof, sequelae of the trauma of the head and epilepsy. In formula (I), R represents hydrogen, halogen, nitro, cyano, hydroxy, optionally substituted lower alkyl, lower alkenyl, lower alkynyl, aralkyl, aryl, lower alkyloxy, cycloalkyl, aralkyloxy, aryloxy, amino, lower acyl, arylcarbonyl, lower alkanesulfonyl, arenesulfonyl, lower alkylthio, carbamoyl, heterocycle, lower alkylene or lower alkenylene; R₁ and R₂, which may be the same or different from each other, represent each hydrogen or optionally substituted lower alkyl; R₃ represents hydrogen, optionally substituted lower alkyl, aryl, aralkyl or heterocycle; R₄ represents optionally substituted lower alkyl, aryl or heterocycle, or alternatively R₃ and R₄ may be combined together to represent lower alkylene; and R₅ and R₆, which may be the same or different from each other, represent each hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkynyl, lower acyl, lower alkyloxycarbonyl or aralkyl.