TV3326, [(
N-propargyl-(3R) aminoindan-5-yl)-ethyl
methyl carbamate] is a novel aminoindan derivative of the selective irreversible
monoamine oxidase (
MAO)-B inhibitor,
rasagiline (N-propargyl-(1R)-aminoindan), possessing both
cholinesterase (ChE) and
MAO-inhibitory activity. In doses of 35-100 micromoles/kg administered orally to rats, it inhibits ChE by 25-40% and antagonises
scopolamine-induced impairments in spatial memory. After daily administration of 75 micromoles/kg for 2 weeks,
TV3326 does not show any motor stimulant effects but significantly reduces immobility in the forced swim test, an action consistent with that of known
antidepressants. This could result from more than 70% inhibition of both
MAO-A and B in the brain that occurs under these conditions, since it is not shared by the S-isomer,
TV3279, which does not block
MAO.
TV3326 also shows selectivity for brain
MAO, even after 2 months of daily administration, with little or no effect on the
enzyme in the intestinal tract and liver. This reduces the likelihood of it producing the "cheese effect" if administered with
tyramine-containing foods or beverages.
TV3326 and
TV3279 protect against
ischemia-induced cytotoxicity in PC12 cells and reduce the oedema, deficits in motor function and memory after
closed head injury in mice. These
neuroprotective effects do not result from
MAO inhibition. The pharmacological actions of
TV3326 could be of clinical importance for the treatment of AD, and the
drug is currently in development for this purpose.