N-propargyl-1-(R)aminoindan (
rasagiline) is a new and selective irreversible
MAO-B inhibitor, currently being considered as the
mesylate salt for potential
therapy in certain
neurological disorders. It has been studied in animal models of cognition and motor dysfunction. Its ability to restore normal motor activity was determined in models of acute
drug-induced dopaminergic dysfunction: Its effects in improving cognition and
memory deficits was studied in adult and senescent rats that had been exposed to prolonged
hypoxia, then subjected to the passive and active avoidance tests. In
alpha-methyl-p-tyrosine (
alpha-MpT)-induced
hypokinesia (100-120 mg/kg, i.p.) pretreatment with
rasagiline at 2.5 mg/kg i.p. restored motor activity to control level. But pretreatment with
reserpine abolished the protective effect of
rasagiline.
Rasagiline at 0.5 mg/kg/day was protective against
alpha-MpT also in
hypoxia-lesioned rats. In
haloperidol-induced
catalepsy in rats (1.5 mg/kg, s.c.) or mice (4-6 mg/kg s.c.),
rasagiline improved recovery of normal locomotion, gait and coordination at 0.4-2.4 mg/kg i.p. and 1.8-1.5 mg/kg i.p., respectively. In
amphetamine-induced stereotypy (0.6 mg/kg s.c.,
rasagiline potentiated this effect at 1.5 mg/kg i.p. In
hypoxia-induced impairment of memory and learning,
rasagiline at 0.32-0.5 mg/kg/day per os improved performance of adult rats in passive and active avoidance, and of senescent rats in active avoidance.
Selegiline was either ineffective or less effective at equivalent doses. Racemic
N-propargyl-1-aminoindan (
AGN-1135), besides being of lower potency, had a different dose-dependency than
rasagiline in antagonizing
haloperidol-induced
catalepsy or
alpha-MpT-induced
hypokinesia. 1-(R)aminoindan ((R)AI), a metabolite of
rasagiline, in relatively high doses produced effects that were distinct in certain respects from those of
rasagiline.