Prodrugs of neuron-selective monoamine oxidase inhibitors: amino acid derivatives of 1-(4-aminophenyl)-2-aminopropanes

Six amino acid derivatives of 1-(4-aminophenyl)-2-aminopropanes and their p arent amines were synthezised and tested for their potency and selectivity in inhibiting monoamine oxidase (MAO) in vitro and in vivo. The amino acid derivatives were 300-1000 times less potent than the parent amines in inhib iting the MAO-A activity in a rat brain mitochondrial preparation in vitro. All compounds, except the (R)-valinamide derivative (22), were potent inhi bitors of MAO in the rat brain in vivo and were, like the parent amines mar kedly more potent within the monoaminergic neurons than in other neurons. T he glycinamide derivative 7 showed the largest difference between intra- an d extra-neuronal inhibition in serotonergic neurons. The time course of the inhibitory effect of 7 in vivo showed that it is a reversible inhibitor wi th a long duration. (C) Elsevier, Paris.