LAZABEMIDE (RO-19-6327), A REVERSIBLE AND HIGHLY SENSITIVE MAO-B INHIBITOR - PRECLINICAL AND CLINICAL FINDINGS

Ro 19-6327 (lazabemide, L), MDL 72974, selegiline, AGN 1135 and MDL 72 145 were investigated for their MAO inhibitory effect in rat tissues i n vitro. The selectivity of MAO-B inhibition of L, selegiline and MDL 72974 was also measured in vitro in human brain tissue as well as ex v ivo in rat brain and liver after acute and subchronic administration. Of all compounds investigated L was the most selective for MAO-B inhib ition under in vitro and ex vivo conditions. In volunteers, L complete ly but reversibly inhibited platelet MAO-B with a dose-dependent durat ion. Clinical trials with L are under way in both Alzheimer's and Park inson's disease (PD).