The potential neuroprotective effects of rasagiline, N-propareyl-1 R-aminoindan, a selective monoamine oxidase-B inhibitor and its inactive enantiomer TVP1022, N-propargyl-1 S-aminoindan were assessed against the sequelae of closed head injury in the mouse, injury was induced in the left hemisphere under ether anaesthesia. Rasagiline (0.2 and 1 mg/kg) or TVP1022 (1 and 2 mg/kg) injected 5 min after injury accelerated the recovery of motor function and spatial memory and reduced the cerebral oedema by about 40-50%, (P < 0.01). The neuroprotective effects on motor function and spatial memory, but not on cerebral oedema, were prevented by scopolamine (0.3 mg/kg). Daily injection of rasagiline (1 mg/kg) from day 3 after injury accelerated the recovery of spatial memory but not motor function. Conclusions: Early administration of rasagiline or TVP1022 can reduce the immediate sequelae of brain injury. The mechanism of action does not appear to involve monoamine oxidase-B inhibition but could be mediated by the maintenance of cholinergic transmission in brain neurons. (C) 1999 Elsevier Science B.V. All rights reserved.