Dopamine D2/D3 receptor

Although DA content is left brain biased in all groups, with saline controls showing a larger asymmetry than all drug-treated groups, Side and Group do not significantly interact. When examining each side independently, it becomes clear that chronic quinpirole treatment causes DA levels in the left brain structure to gradually drop, with the QQ rats showing a notable difference from the saline controls. Conversely, acute Quinpirole only causes a significant (increased) change in right cortical DA levels. Across groups, DOPAC levels are also found to be left brain biased. Nevertheless, no noteworthy Group or interaction effects are discovered. When compared to the QS group or saline controls, rats given acute quinpirole exhibit a specific increase in DA content and decrease in turnover ratio. When compared to the acute quinpirole group, the DOPAC levels of sensitized (QQ) rats are higher. All three of the DA function measures in the striatum also showed significant group differences (DA, F_3,33=6.27, P=0.0020; F_3,33=7.98, P=0.0004; turnover ratio, F_3,33=16.85, P<0.0001), as well as differences in DA function. In comparison to all other groups, the acute quinpirole rats exhibit a significant decrease in both DOPAC and turnover ratio. The turnover ratio increased in both chronic quinpirole groups compared to both chronic saline groups, while DOPAC levels in QQ rats are significantly higher than in any other group[1].

There was a left-brain bias in DA content between groups, and although this asymmetry was greater in the saline control group than in all drug-treated groups, there was no significant interaction between side and group. When considering each side individually, it can be seen that in left brain structures, DA levels gradually decrease with long-term quinpirole treatment, with significant differences between QQ rats and saline controls. In contrast, acute quinpirole only significantly altered (increased) right cortical DA levels. It was found that there was also a left-brain bias in DOPAC levels between groups. However, no significant group or interaction effects were found. Rats receiving acute quinpirole showed a selective increase in DA content and a decrease in turnover rate relative to the saline control or QS groups. However, DOPAC levels were increased in sensitized (QQ) rats compared with the acute quinpirole group. In the striatum, all three measures of DA function also differed significantly between groups (DA, F3,33=6.27, P=0.0020; DOPAC, F3,33=7.98, P=0.0004; turnover rate, F3,33=16.85, P <0.0001). In acute quinpirole rats, DOPAC and turnover rates were significantly reduced relative to all other groups. In QQ rats, DOPAC levels were significantly higher than all other groups, while in terms of turnover rate, both chronic quinpirole groups increased compared with the two chronic saline groups [1].

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Quinpirole, (4 aR-trans)-4, 4a, 5, 6, 7, 8, 8a, 9-octahydro-5-propyl-1 H-pyrazolo [3, 4-g]quinoline, is a dopamine agonist selective for the D2 subtype of dopamine receptors. In rats, quinpirole at doses of 0.3 mg/kg i.p. and higher decreased hypothalamic epinephrine concentrations. The doses required for this effect are only slightly higher than the minimum doses that decreased the concentration of dopamine metabolites in cerebral hemispheres. At higher doses of quinpirole (2-3 mg/kg i.p.), dopamine concentration was increased and norepinephrine concentration was decreased in hypothalamus, and MHPG sulfate (the norepinephrine metabolite) concentration was increased in brain stem and in hypothalamus. All of these neurochemical effects of quinpirole were blocked by pretreatment with spiperone, a dopamine antagonist. The effects were not produced by SKF 38393, a selective D1 agonist, or by the dextrorotatory enantiomer of quinpirole, which lacks D2 agonist activity. The data support the interpretation that quinpirole, by activating D2 receptors, results in a decrease in dopamine metabolites, a decrease in hypothalamic epinephrine concentration, and an increased conversion of norepinephrine to MHPG sulfate in rat brain probably through enhanced norepinephrine release[2].

Rat: After giving injections of either saline or Quinpirole (Hydrochloride) (0.5 mg/kg, s.c., n = 18/condition) to 36 male Long-Evans rats every day for 12 days, the rats are promptly placed in Omnitech activity monitors (60×60×40 cm) for a 90-minute period. n=9/group) of rats in each chronic condition were given saline and half quinpirole on the last test day. Thus, the four groups stood for sensitized Quinpirole (drug) (QQ), acute Quinpirole (SQ), sensitized Quinpirole (no drug) (QS), and saline controls (SS). Thirty minutes following the last injection, every rat is taken out of the activity monitors and brought to a nearby room where it is promptly beheaded. Since acute quinpirole inhibits activity at this time, and chronic quinpirole is linked to marked hyperlocomotion at 30 minutes, this time point is selected to disentangle the behavioral effects of quinpirole between groups[1].

mouse LDLo intraperitoneal 800 mg/kg Journal of Medicinal Chemistry., 26(1112), 1983

[1]. Effects of quinpirole on central dopamine systems in sensitized and non-sensitized rats. Neuroscience. 1998 Apr;83(3):781-9.

[2]. Decrease in hypothalamic epinephrine concentration and other neurochemical changes produced by quinpirole, a dopamine agonist, in rats. J Neural Transm . 1985;61(3-4):161-73.

A dopamine D2/D3 receptor agonist.
The present study examined post mortem changes in central dopaminergic terminal regions following acute or chronic treatment regimens with the dopamine D2/D3 receptor agonist quinpirole, a psychomotor stimulant which induces pronounced behavioural sensitization when given chronically. Drug-induced changes in nucleus accumbens, striatum and amygdala were bilateral in nature, while in prefrontal cortex (medial prefrontal and anterior cingulate combined), left and right brain regions responded differentially to quinpirole. Acute drug treatment increased dopamine tissue levels in nucleus accumbens and right prefrontal cortex, while the dopamine metabolite 3,4-dihydroxyphenylacetic acid, was decreased in amygdala. In contrast, sensitization to quinpirole was associated with decreased dopamine levels in left prefrontal cortex, and increases in 3,4-dihydroxyphenylacetic acid levels in subcortical structures, particularly striatum and amygdala. Additionally, the increase in striatal 3,4-dihydroxyphenylacetic acid in chronic quinpirole animals was independent of drug treatment on the final day of injections. In summary, quinpirole induces a variety of simultaneous, regional changes in dopaminergic function, with the sensitized condition being primarily associated with an up-regulation of subcortical dopamine activity. While the nucleus accumbens and striatum play a well known role in motor activation and sensitized behaviour, it is concluded that the amygdala and prefrontal cortex have significant modulatory influences on these processes, with the role of the prefrontal cortex being asymmetrical in nature. Given the suggested relevance of behavioural sensitization to psychopathological states in humans, parallels are drawn between the present data and clinical findings, particularly in relation to obsessive-compulsive disorder.[1]

C13H22CLN3

255.78688

255.15

C, 61.04; H, 8.67; Cl, 13.86; N, 16.43

85798-08-9

80373-22-4; 85798-08-9 (HCl); 73625-62-4 (2HCl)

55397

White to off-white solid powder

1.07g/cm3

383.9ºC at 760 mmHg

186ºC

1.546

2.738

2

2

2

17

243

2

C(N1CCC[C@@H]2CC3NN=CC=3C[C@@H]12)CC.Cl

HJHVRVJTYPKTHX-HTMVYDOJSA-N

InChI=1S/C13H21N3.ClH/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);1H/t10-,13-;/m1./s1

(4aR,8aR)-5-propyl-1,4,4a,6,7,8,8a,9-octahydropyrazolo[3,4-g]quinoline;hydrochloride

LY-171555; LY 171555; LY171555; (-)Quinpirole hydrochloride; (-)-Quinpirole HCl; (-)Quinpirole HCl; (-)-Quinpirole hydrochloride; 85798-08-9; QUINPIROLE HYDROCHLORIDE; Quinpirole HCl; Quinpirole hydrochloride [USAN]; T6I2W5V2K1; (-) Quinpirole HCl

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: ~50 mg/mL (~195.5 mM)
DMSO: ~27.8 mg/mL (~108.6 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (390.95 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)