Quipazine is a 5-HT agonist that displaces 5-HT3R in rat endothelium with a Ki of 1.4 nM for [3H]GR65630. Quipazine has antiviral effect against SARS-CoV-2 with EC50 of 31.64 μM. Quipazine works as a 5-HT3R agonist in peripheral models and may be utilized to study neurological diseases.

Physicochemical Properties

Molecular Formula	C13H15N3
Molecular Weight	213.28
Exact Mass	213.126
Elemental Analysis	C, 73.21; H, 7.09; N, 19.70
CAS #	4774-24-7
Related CAS #	Quipazine dimaleate;150323-78-7; 4774-24-7; 5786-68-5
PubChem CID	5011
Appearance	Off-white to light yellow solid powder
Density	1.2±0.1 g/cm3
Boiling Point	403.7±25.0 °C at 760 mmHg
Melting Point	120-122 °C(lit.)
Flash Point	198.0±23.2 °C
Vapour Pressure	0.0±0.9 mmHg at 25°C
Index of Refraction	1.629
LogP	1.59
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	1
Heavy Atom Count	16
Complexity	225
Defined Atom Stereocenter Count	0
InChi Key	XRXDAJYKGWNHTQ-UHFFFAOYSA-N
InChi Code	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
Chemical Name	2-piperazin-1-ylquinoline
Synonyms	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)-;
HS Tariff Code	2934.99.9001
Storage	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.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	5-HT receptors
ln Vitro	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].
ln Vivo	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]. 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]
Enzyme Assay	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]
Animal Protocol	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]
Toxicity/Toxicokinetics	mouse LD50 oral 296 mg/kg Drug Development Research., 3(357), 1983 mouse LD50 intraperitoneal 135 mg/kg Journal of Medicinal Chemistry., 28(1394), 1985
References	[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.
Additional Infomation	2-(1-piperazinyl)quinoline is a member of pyridines and a member of piperazines. Quipazine is a piperazine-based nonselective serotonin (5-HT) receptor agonist with antidepressant and oxytocic activities. Quipazine targets and binds to serotonin receptors, particularly to the 5HT2A and 5HT3 receptors. Serotonin receptor activation by quipazine may lead to smooth muscle contraction and antidepressant effects. A pharmacologic congener of serotonin that contracts smooth muscle and has actions similar to those of tricyclic antidepressants. It has been proposed as an oxytocic. The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput x-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied x-ray fragment screening experiments with molecules of low complexity, our screen tested already-approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2. [2] A study has been made of the pharmacology of the 5-hydroxytryptamine (5-HT)-induced depolarization responses that can be recorded extracellularly from the rat isolated cervical vagus nerve. Phenylbiguanide (PBG) and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) were found to mimic the effects of 5-HT on the vagus nerve. Their EC50 values were respectively 2.0 fold and 3.9 fold greater than that of 5-HT. Metoclopramide behaved as a reversible competitive antagonist of depolarization induced by PBG and 2-methyl-5-HT, with pKB values of 6.48 +/- 0.04, respectively. These agreed well with the pKB value of 6.60 +/- 0.04 obtained previously for metoclopramide against 5-HT on the rat vagus nerve. 5-HT, PBG and 2-methyl-5-HT had no demonstrable agonist effects at non-5-HT receptors on the rat vagus nerve. Tropacaine and m-chlorophenylpiperazine were found to behave as reversible competitive antagonists of 5-HT-induced depolarization of the vagus nerve. The pKB values were 6.29 +/- 0.03 and 6.90 +/- 0.03, respectively. Quipazine, MDL 72222 and ICS 205-930 were also shown to be effective antagonists of 5-HT on the vagus nerve. However, although these compounds were highly potent, they all caused a marked concentration-dependent reduction in the amplitude of the maximum response to 5-HT. This behaviour was not consistent with a simple reversible competitive mechanism. The results are discussed with reference to the current classification of mammalian peripheral neuronal 5-HT receptors. [4]

Solubility Data

Solubility (In Vitro)

DMSO : 10 mg/mL (46.89 mM)

Solubility (In Vivo)

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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.6887 mL	23.4434 mL	46.8867 mL
	5 mM	0.9377 mL	4.6887 mL	9.3773 mL
	10 mM	0.4689 mL	2.3443 mL	4.6887 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.