Quinelorane hydrochloride

Comparison of D2 and D3 dopamine receptor affinity of dopaminergic compounds in rat brain.[Pubmed:9600324]

Life Sci. 1998;62(20):1825-31.

This study used quantitative autoradiography to simultaneously evaluate the relative affinities of dopaminergic compounds for dopamine D2 and D3 receptors in rat brain. PD 152255, PD 128907, and l-nafadotride exhibited significantly higher affinity for cerebellar dopamine D3 sites than [3H]quinpirole-labeled sites in caudate/putamen (6.3-, 6.0-, and 2.3-fold, respectively). In contrast, chlorpromazine, risperidone, and domperidone were more potent at striatal dopamine D2 receptors (3.8-, 31-, and 40-fold, respectively). Dopamine, quinelorane, (+)-UH 232, and RS-trans-7-OH-PIPAT exhibited relatively little D2/D3 selectivity.

Effects of the selective dopaminergic D2 agonist quinelorane on the activity of dopaminergic and noradrenergic neurons projecting to the diencephalon of the rat.[Pubmed:7906734]

J Pharmacol Exp Ther. 1994 Feb;268(2):645-52.

The purpose of the present study was to characterize dopaminergic D2 receptor-mediated regulation of catecholaminergic neurons in the diencephalon by examining the acute effects of the potent and selective D2 agonist quinelorane (LY163502; trans-(-)-5,5a,6,7,8,9,9a,10-octahydro-6-propylpyrimido [4,5-g] quinolin-2-amine dihydrochloride dihydrate) on concentrations of 3,4-dihydroxyphenylacetic acid, dopamine, 3-methoxy-4-hydroxyphenylethyleneglycol and norepinephrine in the dorsomedial nucleus of the hypothalamus and horizontal limb of the diagonal band of Broca of intact and norepinephrine-depleted male rats. For comparative purposes, various other diencephalic brain regions and the nucleus accumbens were also examined. The results of this study reveal that quinelorane decreases the activity of dopaminergic neurons in the nucleus accumbens, horizontal limb of the diagonal band of Broca and dorsomedial nucleus of the hypothalamus, whereas it increases the activity of noradrenergic neurons projecting to the dorsomedial nucleus of the hypothalamus, but not the horizontal limb of the diagonal band of Broca. These inhibitory and stimulatory actions of quinelorane are blocked by or reverse the effects of the D2-selective antagonist raclopride, indicating that quinelorane is acting at D2 receptors. Taken together, these results indicate that quinelorane inhibits DA neurons within the diencephalon, whereas it activates a subpopulation of noradrenergic neurons projecting to this brain region.

Preclinical studies on quinelorane, a potent and highly selective D2-dopaminergic agonist.[Pubmed:2526214]

J Pharmacol Exp Ther. 1989 Jul;250(1):227-35.

Quinelorane (LY163502) has the endocrine, neurochemical and behavioral profile of a potent and highly selective D2-dopaminergic agonist. The administration of quinelorane produced dose-related decreases in serum prolactin concentration of reserpinized, male rats and increases in serum corticosterone concentration of male rats. The minimum effective doses (MED) for these effects were 10 and 30 micrograms/kg i.p., respectively. Quinelorane induced increases in 3-methoxy-4-hydroxyphenylglycol-sulfate levels in the brain stem (MED, 30 micrograms/kg i.p.) and decreases in hypothalamic epinephrine levels (MED, 100 micrograms/kg i.p.) in male rats as determined by high-pressure liquid chromatography with electrochemical detection methods. Quinelorane induced increases in extracellular ascorbic acid as determined by in vivo voltammetry in the nucleus accumbens and striatum of male rats. Quinelorane produced concentration-dependent suppression of K+-evoked release of acetylcholine from superfused caudate slices, with an IC50 of approximately 10(-8)M. Quinelorane administration produced dose-related increases in compulsive, contralateral turning in male rats with unilateral nigrostriatal lesions and increases in locomotor activity and stereotypic behavior in male rats. In dogs, quinelorane administration produced dose-related increases in emetic response with an ED50 of 7 micrograms/kg i.v. Quinelorane administration also produced dose-related decreases in the striatal concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic (MED, 1 microgram/kg i.p. for both metabolites) as determined by high-pressure liquid chromatography with electrochemical detection methods and decreases in extracellular concentrations of homovanillic acid in the nucleus accumbens and striatum as determined by in vivo voltammetry., Quinelorane produced concentration-dependent decreases in K+-evoked dopamine release from superfused striatal slices (IC50 = 3 X 10(-9) M).(ABSTRACT TRUNCATED AT 250 WORDS)