(−)-Quinpirole hydrochloride 

The putative D₂ dopamine receptor agonist quinpirole (LY 171,555) is the most widely used D₂ agonist in in vivo and in vitro studies Active enantiomer of (±)-quinpirole. Quinpirole is a dopamine agonist with high affinity for the D₂ and D₃ dopamine receptor subtypes. Specific [³H]quinpirole binding in rat brain was saturable, and dependent on temperature, membrane concentration, sodium concentration and guanine nucleotides. Saturation analysis revealed high affinity binding characteristics (K_D = 2.3 +/- 0.3 nM) which were confirmed by association-dissociation kinetics. The regional distribution of [³H]quinpirole binding sites roughly paralleled the distribution of [³H]spiperone binding sites, with greatest densities present in the striatum, nucleus accumbens and olfactory tubercles. 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. 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. 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.

Manufactured and sold with the permission of Eli Lilly and Company.

≥98% (HPLC)

solid

[α]25/D −124.5°, c = 0.4 in H₂O(lit.)

white

0.1 M HCl: 23 mg/mL

H₂O: 7.3 mg/mL

human ... DRD2(1813), DRD3(1814)

−20°C

Munro, L.J., and Kokkinidis, L., Infusion of quinpirole and muscimol into the ventral tegmental area inhibits fear-potentiated startle: implications for the role of dopaminine fear expression. Brain Res. 746, 231-238, (1997) abstract

Kebabian, et al., Compounds selective for dopamine receptor subtypes. Drug Discov. Today 2, 333-340, (1997)

Zaworski, P.G., Efficient functional coupling of the human D3 dopamine receptor to G(o) subtype of G proteins in SH-SY5Y cells. Br. J. Pharmacol. 128, 1181, (1999) abstract

Sanger, D.J.D., Evidence for a role for dopamine D3 receptors in the effects of dopamine agonists on operant behaviour in rats. Behav. Pharmacol. 7, 477-482, (1996) abstract

Sartania, N., and Strange, P.G., Role of conserved serine residues in the interaction of agonists with D3 dopamine receptors. J. Neurochem. 72, 2621-2624, (1999) abstract

Rosenzweig-Lipson, S., and Barrett, J.E., K-Channel blockers attenuate the presynaptic effects of the D₂/D₃ agonist quinpirole in monkeys. Pharmacol. Biochem. Behav. 51, 843-848, (1995) abstract

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UR0809270