Invited Symposium: MAOIs: Mulptiple Effects and Sites of Action


[3H]Quinpirole and D2-like Receptors

MAOIs Inhibit [3H]Quinpirole Binding

MAO is not Involved in MQB

The MQB Site May be a D2-like Receptor



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MAOIs: Interactions at Dopamine Receptors?

Levant, B (Dept. of Pharmacology, University of Kansas Medical Center, USA)
Moehlenkamp, JD (Dept. of Pharmacology, University of Kansas Medical Center, USA)
Bancroft, GN (Dept. of Pharmacology, University of Kansas Medical Center, USA)
Morgan, KA (Dept. of Pharmacology, University of Kansas Medical Center, USA)

Contact Person: Beth Levant (blevant@kumc.edu)


[3H]Quinpirole is a dopamine agonist with high affinity for D2-like dopamine receptors. Surprisingly, a number of non-dopaminergic compounds, most notably monoamine oxidase inhibitors (MAOIs), inhibit the binding of [3H]quinpirole, but not other D2-like agonists and antagonists, in rat striatal membranes by a mechanism that does not involve the enzymatic activity of MAO. Clorgyline and Ro 41-1049 exhibited > 3,000-fold higher affinity for [3H]quinpirole binding over [3H]spiperone. Antidepressant MAOI's inhibited [3H]quinpirole binding with the following rank order of potency: phenelzine > pargyline > tranylcypromine > isocarboxazid > nialamide > moclobemide. The regional distribution of MAOI-displaceable [3H]quinpirole binding (MQB) in brain paralleled that of D2-like receptors with the greatest densities in striatum and nucleus accumbens. Subcellular distribution of MQB also paralleled dopaminergic [3H]quinpirole binding. Furthermore, the rank order of potencies of MQB correlated poorly the potencies of MAOIs at sigma, imidazoline, or dopamine uptake sites. Taken together, these data suggest the existence of a novel MQB site in rat brain that is either labeled by [3H]quinpirole in addition to dopamine receptors or which modulates [3H]quinpirole binding at D2-like receptors. Supported by NARSAD.

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Presentation Number SAlevant0103
Keywords: MAOI, dopamine receptor, quinpirole, brain, rat

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Levant, B; Moehlenkamp, JD; Bancroft, GN; Morgan, KA; (1998). MAOIs: Interactions at Dopamine Receptors?. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/levant/levant0103/index.html
© 1998 Author(s) Hold Copyright