title: Modulation of [3H]quinpirole binding in brain by monoamine oxidase inhibitors: evidence for a potential novel binding site.
abstract: [3H]Quinpirole is a dopamine agonist with high affinity for the D2 and D3 dopamine receptor subtypes. A variety of drugs, most notably monoamine oxidase inhibitors (MAOls), inhibit the binding of [3H]quinpirole, but not [3H]spiperone or [3H](-)N-n-Propylnorapomorphine, in rat striatal membranes by a mechanism that does not appear to involve the enzymatic activity of MAO. This study extends the characterization of MAOI-displaceable [3H]quinpirole binding in rat brain. Clinically antidepressant MAOIs exhibited selectivity between sites labeled by [3H]quinpirole and [3H]spiperone as did a number of structurally related propargylamines and N-acylethylenediamine derivatives and other drugs such as debrisoquin and phenylbiguanide. The MAOIs clorgyline and Ro 41-1049 were the most potent. Anti-depressant MAOIs inhibited [3H]quinpirole binding with the following rank order of potency: phenelzine > pargyline > tranyl-cypromine > isocarboxazid > nialamide > moclobemide. In striatal membranes, MAOI Ro 41-1049 inhibited [3H]quinpirole binding with similar potency at a variety of incubation temperatures (4-37 degrees C), assay tissue concentrations (5-20 mg original wet weight/ml), and time points (2 min-4 hr) and in the presence or absence of K+, Mg2+, Ca2+ ions, ascorbate, EDTA and NaCl. The regional distribution of Ro 41-1049-displaceable [3H]quinpirole binding in brain paralleled that of D2-like receptors. These data suggest that MAOIs interact with a novel binding site that is labeled by [3H]quinpirole or that modulates [3H]quinpirole binding. This site may be associated with D2-like dopamine receptors.
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, USA.
authors.forename: B
authors.initials: B
authors.lastname: Levant
authors.forename: J D
authors.initials: JD
authors.lastname: Moehlenkamp
authors.forename: K A
authors.initials: KA
authors.lastname: Morgan
authors.forename: N L
authors.initials: NL
authors.lastname: Leonard
authors.forename: C C
authors.initials: CC
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D013134:Spiperone / Q000494:pharmacology
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D019257:Quinpirole; D013134:Spiperone