title: Binding of [3H]Ro 16-6491, a reversible inhibitor of monoamine oxidase type B, to human brain mitochondria and platelet membranes.
abstract: The reversible inhibitor of monoamine oxidase type B (MAO-B) [3H]Ro 16-6491 binds specifically and with high affinity to a single population of binding sites in human frontal cortex crude mitochondria and platelet membranes. In both tissues binding equilibrium was reached after 1 h incubation at 20 degrees C. Dissociation of bound radioactivity was relatively fast at 20 degrees C (t1/2 = 90-120 min) whereas at 0 degrees C [3H]Ro 16-6491 showed the characteristics of a slowly dissociating ligand. Inhibitors and substrates of MAO-B inhibited binding of [3H]Ro 16-6491, whereas MAO-A blockers were much less potent. Ro 16-6491 was also a substrate for MAO-B and a stable unidentified intermediate of the oxidation of Ro 16-6491 possessing high affinity for the enzyme may account for the marked MAO-B inhibitory effect of the drug. According to this hypothesis Ro 16-6491 would behave as a mechanism-based reversible inhibitor. In conclusion, [3H]Ro 16-6491 binds selectively to MAO-B and represents an excellent new radioligand probe for studying the regional tissue distribution of this enzyme in normal and pathological conditions.
mesh_terms: D001549:Benzamides / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism*
chemical_list: D001549:Benzamides; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; C051040:Ro 16-6491; D008995:Monoamine Oxidase