No abstract

No abstract

1 Previous studies with indolyl derivatives as monoamine oxidase (MAO) inhibitors have shown the relevance of the indole structure for recognition by the active site of this enzyme. We now report a new series of molecules with structural features which determine the selectivity of MAO inhibition. 2 A benzyloxy group attached at position 5 of the indole ring is critical for this selective behaviour. Amongst all of these benzyloxy-indolyl methylamines, N-(2-propynyl)-2-(5-benzyloxyindol)methylamine FA-73 was the most potent MAO-B`suicide' inhibitor studied. 3 The K i values for MAO-A and MAO-B were 800+60 and 0.75+0.15 nM, respectively. These data represent a selectivity value of 1066 for MAO-B, being 48 times more selective than L-deprenyl (K i values of 376+0.032 and 16.8+0.1 nM for MAO A and MAO-B, respectively). The IC 50 values for dopamine uptake in striatal synaptosomal fractions from rats were 150+8 mM for FA-73 and 68+10 mM for L-deprenyl whereas in human caudate tissue the IC 50 values were 0.36+0.015 mM for FA-73 and 0.10+0.007 mM for L-deprenyl. Moreover, mouse brain MAO-B activity was 90% ex vivo inhibited by both compounds 1 h after 4 mg kg 71 adminstration, MAO-A activity was not a ected. 4 These novel molecules should provide a better understanding of the active site of monoamine oxidase and could be the starting point for the design of further selective, non-amphetamine-like MAO-B inhibitors with therapeutic potential for the treatment of neurological disorders.

No abstract

No abstract