MODULATION OF [H-3] QUINPIROLE BINDING IN BRAIN BY MONOAMINE-OXIDASE INHIBITORS - EVIDENCE FOR A POTENTIAL NOVEL BINDING-SITE

[H-3]Quinpirole is a dopamine agonist with high affinity for the D-2 a nd D-3 dopamine receptor subtypes. A variety of drugs, most notably mo noamine oxidase inhibitors (MAOIs), inhibit the binding of [H-3]quinpi role, but not [H-3]spiperone or [H-3](-)-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 [H-3]quinpirole binding in rat brain. Clinically antidepressant MAOIs exhibited selectivity between sites labeled by [ H-3]quinpirole and [H-3]spiperone as did a number of structurally rela ted propargylamines and N-acylethylenediamine derivatives and other dr ugs such as debrisoquin and phenylbiguanide. The MAOIs clorgyline and Ro 41-1049 were the most potent. Antidepressant MAOIs inhibited [H-3]q uinpirole binding with the following rank order of potency: phenelzine > pargyline > tranylcypromine > isocarboxazid > nialamide > moclobemi de. In striatal membranes, MAOI Ro 41-1049 inhibited [H-3]quinpirole b inding with similar potency at a variety of incubation temperatures (4 -37 degrees C), assay tissue concentrations (5-20 mg original wet weig ht/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 distributi on of Ro 41-1049-displaceable [H-3]quinpirole binding in brain paralle led that of D-2-like receptors. These data suggest that MAOIs interact with a novel binding site that is labeled by [H-3]quinpirole or that modulates [H-3]quinpirole binding. This site may be associated with D- 2-like dopamine receptors.