5-HT receptors

Quipazine has 230 nM Ki values for 5-HT1 and 5-HT2 binding potency [3]. With a Ki value of 1.4 nM, quipazine replaces [3H]GR65630 of 5-HT3R in rat endothelium [3]. The rat vagus nerve is antagonistically affected by quipazine; its pIC50 values for inhibition of 5-HT release, 5-HT2, and 5-HT1 are 6.17, 6.49, and 6.1, respectively [4].

In male and female rats, quipazine (2.5, 5, and 7.5 mg/kg, once each; i.p.) influences the nutritional self-selection of various macronutrient diets [1].

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Macronutrient intakes, 2h and 12h, following administration of a selective 5-HT3 agonist, quipazine, N methyl, dimaleate (QUIPAZINE; 2.5, 5.0 and 7.5 mg/kg, i.p.) at dark onset were examined in three groups of adult male and female Wistar rats fed different sources of the three macronutrients: Group 1 (casein, corn starch, safflower oil), Group 2 (egg protein, corn starch/sucrose, lard) and Group S (casein hydrolysate, maltose dextrin, butter). QUIPAZINE decreased total food intake only in female rats from Group 1 (2 h) at a dose of 7.5 mg/kg and Group 2 (2h and 12h) with doses of 2.5 and 7.5 mg/kg. Intakes from corn starch and corn starch/sucrose diet (12h) were reduced in male and female rats, respectively, with doses of 2.5 and 7.5 mg/kg of QUIPAZINE. In conclusion, when provided with different sources of the three macronutrients, quipazine injection reduces specifically carbohydrate ingestion from corn starch-containing diets in male and female rats. Thus, the nature of the macronutrient source is of major importance to assess the effect of a drug on nutrient-specific selection. [1]

Arylpiperazines, such as 1-(3-trifluoromethylphenyl)piperazine (TFMPP) and its chloro analogue mCPP, are 5-HT1 agonists, whereas quipazine, i.e., 2-(1-piperazino)quinoline, appears to be a 5-HT2 agonist. Radioligand binding studies using rat cortical membrane homogenates and drug discrimination studies using rats trained to discriminate a 5-HT1 agonist (i.e., TFMPP) or a 5-HT2 agonist (i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM)) from saline reveal that quipazine and its 1-deaza analogue 2-naphthylpiperazine (2-NP) bind at 5-HT1 and 5-HT2 sites but produce stimulus effects similar to those of DOM. A structurally related compound, 1-naphthylpiperazine (1-NP), possesses a high affinity for 5-HT1 (Ki = 5 nM) and 5-HT2 (Ki = 18 nM) sites. 1-NP produces stimulus effects similar to those of TFMPP and is able to antagonize the stimulus effects produced by DOM. The present results suggest that the unsubstituted benzene ring of quipazine, and of its 1-deaza analogue 2-naphthylpiperazine, makes a significant contribution to the binding of these agents to 5-HT2 sites and, more importantly, may account for their 5-HT2 agonist properties. [3]

Rats were given 10 days to adapt to the diets and the environment. For the initial 3 days of adaptation rats were allowed ad libitum access to the diets. In order to habituate rats to a similar 4-h food deprivation as during the injection days, rats were subsequently adapted to a daily 4-h food deprivation period between 1600h and 2000h during the remaining seven days of adaptation. Body weights, water and macronutrient intakes during the 12-h dark phase were measured daily during the 10 days of adaptation. On injection days, following a 4-h food deprivation, rats from the three dietary groups received i.p. injections at dark onset (2000h) of either physiological saline (0
9% NaCl) or Quipazine, N-methyl, dimaleate (QUIPAZINE, RBI) dissolved in physiological saline. Macronutrient and water intakes were measured at 2 h and 12 h following injections. Drug doses were given in the following order: saline, 2
5 mg/kg, 5
0 mg/kg and 7
5 mg/kg Quipazine. In order to avoid possible down regulation of 5-HT receptors following higher doses of Quipazine, the drug dosage was administered in ascending order rather than counterbalanced. Drug injection days were separated by 48 h. Basal self-selection profiles for each of the three dietary groups were resumed before subsequent injections. Contrast comparisons revealed no difference between 12 h basal macronutrient intakes for each of the three dietary groups and 12 h macronutrient intakes on washout days. [1]

The oral LD50 in mice was 296 mg/kg, Drug Development Research, 3(357), 1983; the intraperitoneal LD50 in mice was 135 mg/kg, Journal of Pharmaceutical Chemistry, 28(1394), 1985.

[1]. Effect of quipazine, a selective 5-HT3 agonist, on dietary self-selection of different macronutrient diets in male and female rats. Appetite. 2000 Jun;34(3):313-25.

[2]. X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease. Science. 2021 May 7;372(6542):642-646.

[3]. 5-HT1 and 5-HT2 binding characteristics of some quipazine analogues. J Med Chem. 1986 Nov;29(11):2375-80.

[4]. Ireland SJ, Tyers MB. Pharmacological characterization of 5-hydroxytryptamine-induced depolarization of the rat isolated vagus nerve. Br J Pharmacol. 1987 Jan;90(1):229-38.

2-(1-piperazinyl)quinoline belongs to the pyridine and piperazine classes of compounds. Quinapazine is a piperazine-based non-selective serotonin (5-HT) receptor agonist with antidepressant and oxytocin-producing activities. Quinapazine targets and binds to serotonin receptors, particularly 5-HT2A and 5-HT3 receptors. Activation of serotonin receptors by quinapazine may lead to smooth muscle contraction and antidepressant effects. It is a pharmacological analog of serotonin that contracts smooth muscle, acting similarly to tricyclic antidepressants. It was once considered an oxytocin. Coronavirus disease (COVID-19) caused by SARS-CoV-2 is causing immense human suffering. To date, there are no effective drugs that directly treat the disease. To search for drugs to combat COVID-19, we performed high-throughput X-ray crystallography screening on two drug repositioning libraries, targeting the major protease (Mpro) of SARS-CoV-2, which is crucial for viral replication. Unlike commonly used low-complexity molecular X-ray fragment screening experiments, our screening tested approved drugs and drugs undergoing clinical trials. From the three-dimensional protein structure, we identified 37 compounds that bind to Mpro. In subsequent cell-based virulence reduction experiments, one peptide mimic and six non-peptide compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites that are ideal targets for developing anti-SARS-CoV-2 drugs. [2]

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A study investigated the pharmacology of 5-hydroxytryptamine (5-HT)-induced depolarization, which was derived from extracellular recordings of isolated rat cervical vagus nerves. Phenylenetidine (PBG) and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) were found to mimic the effect of 5-hydroxytryptamine (5-HT) on the vagus nerve. Their EC50 values were 2.0 and 3.9 times that of 5-HT, respectively. Metoclopramide, as a reversible competitive antagonist of PBG and 2-methyl-5-HT-induced depolarization, had a pKB value of 6.48 ± 0.04. These results are highly consistent with the previously reported pKB value of 6.60 ± 0.04 for metoclopramide on 5-HT receptors in the rat vagus nerve. 5-HT, PBG, and 2-methyl-5-HT did not show significant agonistic effects on non-5-HT receptors in the rat vagus nerve. Topivacaine and m-chlorophenylpiperazine were found to be reversible competitive antagonists of 5-HT-induced vagal depolarization, with pKB values of 6.29 ± 0.03 and 6.90 ± 0.03, respectively. Quinapazine, MDL 72222, and ICS 205-930 have also been shown to be effective antagonists of 5-HT in the vagus nerve. However, despite their high potency, these compounds all resulted in a significant reduction in the maximum 5-HT response amplitude in a concentration-dependent manner. This phenomenon is inconsistent with a simple reversible competition mechanism. These results are discussed in conjunction with the existing classification of 5-HT receptors in mammalian peripheral neurons. [4]

C13H15N3

213.28

213.126

C, 73.21; H, 7.09; N, 19.70

4774-24-7

Quipazine dimaleate;150323-78-7; 4774-24-7; 5786-68-5

5011

Off-white to light yellow solid powder

1.2±0.1 g/cm3

403.7±25.0 °C at 760 mmHg

120-122 °C(lit.)

198.0±23.2 °C

0.0±0.9 mmHg at 25°C

1.629

1.59

1

3

1

16

225

0

XRXDAJYKGWNHTQ-UHFFFAOYSA-N

InChI=1S/C13H15N3/c1-2-4-12-11(3-1)5-6-13(15-12)16-9-7-14-8-10-16/h1-6,14H,7-10H2

2-piperazin-1-ylquinoline

quipazine; 2-Piperazin-1-yl-quinoline; 4774-24-7; 2-(piperazin-1-yl)quinoline; 2-Piperazin-1-ylquinoline; 2-(1-Piperazinyl)quinoline; Quipazine [INN]; Quinoline, 2-(1-piperazinyl)-;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

DMSO : 10 mg/mL (46.89 mM)

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.)