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 72145 were investigated for their MAO inhibitory effect in rat tissues in 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 vivo in rat brain and liver after acute and subchronic administration. Of all compounds investigated L was the most selective for MAO-B inhibition under in vitro and ex vivo conditions. In volunteers, L completely but reversibly inhibited platelet MAO-B with a dose-dependent duration. Clinical trials with L are under way in both Alzheimer's and Parkinson's disease (PD).
Henriot
S
S
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Kuhn
C
C
Kettler
R
R
Da Prada
M
M
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D001921:Brain / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008099:Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010848:Picolinic Acids / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; C059303:lazabemide; D008995:Monoamine Oxidase