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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H21N3
Molecular Weight 219.3259
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of QUINPIROLE

SMILES

[H][C@]12CCCN(CCC)[C@]1([H])CC3=C(C2)NN=C3

InChI

InChIKey=FTSUPYGMFAPCFZ-ZWNOBZJWSA-N
InChI=1S/C13H21N3/c1-2-5-16-6-3-4-10-7-12-11(8-13(10)16)9-14-15-12/h9-10,13H,2-8H2,1H3,(H,14,15)/t10-,13-/m1/s1

HIDE SMILES / InChI

Description

Quinpirole (LY 171,555) is a psychoactive drug and research chemical which acts as a selective D2 and D3 receptor agonist. Quinpirole is the most widely used D2 agonist in in vivo and in vitro studies. Specific 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 (KD = 2.3 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. Quinpirole has been shown to increase locomotion and sniffing behavior in mice and induces compulsive behavior symptomatic of obsessive compulsive disorder in rats.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
9.8 nM [EC50]
19.0 nM [EC50]
9.9 nM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
0.5 mg/kg (two injections/week)
Route of Administration: Other
In Vitro Use Guide
Adult, male, Sprague-Dawley rats (200-250g; Harlan Labs, Indianapolis, IN) were sacrificed by decapitation, the brains rapidly removed and dissected on ice. Striatal tissue was homogenized in 30 vol. ice-cold 0.32 M sucrose using a glass homogenizer and Teflon pestle. The crude nuclear fraction (P1), the pellet formed from centrifugation of the pellet at 1,000 x g for 10 mitt; the crude synaptosomal fraction (P2), the pellet formed by the centrifugation of the resulting supernatant at 20,000 x g for 30 min; Subfractionation of the crude synaptosomal fraction (P2) was performed by centrifugation of freshly prepared P2 fraction suspended in 0.32 M sucrose over a discontinuous gradient of 0.8 M and 1.2 M sucrose at 110,000 x g for 70 min. Three subfractions were collected. The myelin fraction (P2A) was collected at the 0.32 M/O.8 M sucrose interface; the synaptosomal fraction (P2B) at the 0.8 /1.2 M sucrose interface; and the mitochondrial fraction (P2C), the final pellet. All resulting fractions were resuspended in assay buffer and centrifuged at 100,000 x g for 30 min. The resulting pellets were used for receptor binding assays. The final fraction pellets were resuspended in assay buffer (50 mM Tris-HCl, 5 mM KCI, 2 mM MgCl2, and 2 mM CaCl2, pH 7.4 at 23°C) to yield a final protein concentration of 400 mkg/tube. Binding assays were performed in duplicate in disposable polystyrene tubes. Saturation analyses were performed in the major subcellular fractions to determine radioligand affinity. For saturation analyses, eight concentrations of [3H]quinpirole (43 Ci/mmol; NEN DuPont Research Products, Boston, MA) were used (0.1 to 30 nM). Because [3H]quinpirole exhibited similar affinity in the major subcellular fractions, single point analyses were used for subsequent experiments. For single point studies, the final concentration of [3H]quinpirole was ~2 nM Binding was initiated by the addition of resuspended subcellular fractionate. The total assay volume was 0.5 ml. Tubes were incubated at 23°C for 4 h