title: Monoamine oxidase inhibitors inhibit [3H]quinpirole binding in rat striatal membranes.
abstract: This study describes interactions of monoamine oxidase inhibitors at binding sites labeled by [3H]quinpirole, a putatively selective ligand for dopamine D2-like receptors, in in vitro binding assays in rat brain. Monoamine oxidase inhibitors potently and competitively inhibited equilibrium binding of [3H]quinpirole in homogenate binding assays with the following rank order of potencies: clorgyline > or = Ro 41-1049 > pargyline > (-)-deprenyl > (+)-deprenyl > Ro 16-6491 > iproniazid. This rank order of potencies does not correlate with the potencies of these drugs at monoamine oxidase-A or monoamine oxidase-B, sigma site(s) or dopamine receptors. Monoamine oxidase inhibitors did not alter the ability of quinpirole to compete for [3H]spiperone binding. Quinpirole did not inhibit monoamine oxidase-A or monoamine oxidase-B activity and had low affinity (200 nM) for sigma site(s). These data suggest a potential novel binding site for [3H]quinpirole in rat brain and/or an alternative site of action for the antidepressant effects of monoamine oxidase inhibitors.
authors.affiliation: Central Nervous System Diseases Research The DuPont Merck Pharmaceutical Company, Wilmington, DE 19880-0400.
authors.forename: B
authors.initials: B
authors.lastname: Levant
authors.forename: D E
authors.initials: DE
authors.lastname: Grigoriadis
authors.forename: E B
authors.initials: EB
authors.lastname: DeSouza
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism*; D004873:Ergolines / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D004873:Ergolines; D008996:Monoamine Oxidase Inhibitors; D017448:Receptors, Dopamine D2; D017480:Receptors, sigma; D019257:Quinpirole; D013134:Spiperone; C009074:N-n-propylnorapomorphine; C012134:SK&F 10047; D008995:Monoamine Oxidase; D010620:Phenazocine; D001058:Apomorphine