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, F3,33=6.27, P=0.0020; F3,33=7.98, P=0.0004; turnover ratio, F3,33=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.

Quinpirole is a pyrazoloquinoline that is (4aR,8aR)-4,4a,5,6,7,8,8a,9-octahydro-1H-pyrazolo[3,4-g]quinoline substituted by a propyl group at position 5. It acts as a dopamine agonist. It has a role as a dopamine agonist.
A dopamine D2/D3 receptor agonist.

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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]

C13H21N3

219.32594

219.174

C, 71.19; H, 9.65; N, 19.16

80373-22-4

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

54562

Typically exists as solid at room temperature

1.936

1

2

2

16

243

2

CCCN1CCC[C@@H]2CC3NN=CC=3C[C@@H]12

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

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

QUINPIROLE; 80373-22-4; Quinpirole [INN]; Quinpirolum; Quinpirol; CHEBI:75401; 1H-Pyrazolo(3,4-g)quinoline, 4,4a,5,6,7,8,8a,9-octahydro-5-propyl-, (4aR-trans)-; (4aR,8aR)-5-propyl-1,4,4a,6,7,8,8a,9-octahydropyrazolo[3,4-g]quinoline;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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