@article {Levant145, author = {B Levant and J D Moehlenkamp and K A Morgan and N L Leonard and C C Cheng}, title = {Modulation of [3H]quinpirole binding in brain by monoamine oxidase inhibitors: evidence for a potential novel binding site.}, volume = {278}, number = {1}, pages = {145--153}, year = {1996}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, 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.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/278/1/145}, eprint = {https://jpet.aspetjournals.org/content/278/1/145.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }