Vabicaserin HCl's primary target is the 5-hydroxytryptamine 2C (5-HT2C) receptor, a G protein-coupled receptor. It acts as a selective agonist at this receptor, with an EC50 of 8 nM.

Vabicaserin, with a Ki value of 3 nM, is more selective than many serotonins and has 50 times stronger receptors for noradrenergic and dopaminergic medicines than 125I-(2,5-dimethoxy)phenylisopropylamine at the human 5-HT2C receptor site in the cell membrane of Chinese hamster ovary. Using [3H]5HT, it was found that the binding affinity for the human 5-HT2B receptor subtype was 14 nM. Depending on the amount of receptor expression in transfected cells, vabicaserin can exhibit 5-HT2A receptor antagonism, 5-HT2B antagonist, or partial agonist action. It is a powerful full agonist (EC50, 8 nM; Emax, 100%) that increases 5-HT2C receptor-coupled calcium mobilization. Vabicaserin binds to the 5-HT2C antagonist binding site (22 nM) with modest affinity at the [3H]mesulergine-labeled site. Further studies on binding have demonstrated that vabicaserin binds to the 5-HT2B and 5-HT1A receptors with an affinity of 14 and 112 nM, respectively [1].
In vitro, Vabicaserin HCl demonstrates high selectivity for the 5-HT2C receptor. It shows a Ki value of 3 nM at the human 5-HT2C receptor. It has over 50-fold selectivity for 5-HT2C over noradrenergic and dopaminergic receptors.

Less than 19% of the total plasma radioactivity in mice, rats, and dogs was accounted for by unchanged drug following single oral doses of 50, 5, and 15 mg/kg [14C]Vabicaserin at all time periods analyzed. 20% and 35% correspondingly. Rat plasma does not contain carbamoylglucuronide (CG) following a single [14C]Vabicaserin dosage, however it does contribute for roughly 7% to 36% of radioactivity in mouse plasma and roughly 2% to 28% in dog plasma. found. Nevertheless, following successive doses of vabicaserin at larger doses, CG was detected in rat plasma; based on steady-state AUC0-24 values, it was roughly 20 times lower than vabicaserin. Following a single [14C]Vabicaserin dosage, the estimated plasma AUC0–24 ratio of CG to parent drug was 1.5 in mice and 1.7 in dogs, respectively. The steady state plasma AUC0-24 ratios for CG and varbcaserin at the doses employed for safety assessment were slightly greater (1.8-4.0) in dogs and lower (0.2-0.6) in humans when compared to single-dose values. While CG was not found in mouse or rat urine following a single [14C]Vabicaserin dosage, it was found in dog urine at amounts comparable to those of the parent medication. Rats given 5 mg/kg [14C]Vabicaserin had radioactivity in their bile collections that represented 19% and 24% of the dose given to the males and females, respectively, from 0 to 24 hours. CG accounted for an average of up to 30% of the bile radioactivity in male rats and an average of up to 15% in female rats, despite the fact that it was not found in the urine or feces of rats following a single oral dosage. In monkeys given a single oral dose of 25 mg/kg vabicaserin, CG decreased from 2 to 24 hours post-dosing; however, during 24 hours, the amount of CG decreased in comparison to vabicaserin. The concentrations of plasma were higher than those of vabikaserin. The ratio was 17.5 at two hours and 1.7 at twenty-four hours after dosage. The primary metabolite in monkeys is CG, as evidenced by the 12:1 ratio of CG to vabicaserin AUC0-24 [2].
In vivo, Vabicaserin HCl was studied for its potential to treat schizophrenia. Specific in vivo efficacy data in animal models is not detailed in the search results, but its development as an antipsychotic suggests it demonstrated central nervous system activity.

The standard assay for measuring 5-HT2C receptor agonism involves a cell-based functional assay, such as a calcium mobilization assay or a reporter gene assay. CHO cells expressing the human 5-HT2C receptor are used. Cells are loaded with a calcium-sensitive dye, and the increase in intracellular calcium upon agonist binding is measured.

For cellular assays, Chinese hamster ovary (CHO) cells expressing the human 5-HT2C receptor are cultured in standard media. Cells are treated with varying concentrations of Vabicaserin HCl. The functional response, such as calcium flux or inositol phosphate accumulation, is measured to determine the EC50 value.

In vivo, Vabicaserin HCl would be administered orally or intraperitoneally to animal models. Behavioral assays relevant to schizophrenia, such as prepulse inhibition or locomotor activity, would be used to assess the compound's efficacy.

Vabicaserin HCl has a molecular weight of 264.14 g/mol. It is soluble in DMSO (≥15.95 mg/mL) and water (≥30.5 mg/mL). Its hydrochloride salt form is used to enhance aqueous solubility.

Specific toxicity data for Vabicaserin HCl is not detailed in the search results. As a 5-HT2C agonist, potential side effects may include those related to serotonin receptor activation.

[1]. Characterization of Vabicaserin (SCA-136), a selective 5-hydroxytryptamine 2C receptor agonist. J Pharmacol Exp Ther. 2011 Jun;337(3):673-80.

[2]. Species differences in the formation of Vabicaserin carbamoyl glucuronide. Drug Metab Dispos. 2010 Apr;38(4):581-90.

Vabicaserin HCl was developed for the treatment of schizophrenia. However, its development appears to have been discontinued, as it is not an approved drug. It remains a research tool for studying the 5-HT2C receptor.

C15H21CLN2

264.793642759323

264.139

887258-94-8

887258-95-9;887258-94-8 (HCl);

11521821

Light yellow to yellow solid powder

2

2

0

18

291

2

C12C=CC=C3C=1N(CCNC3)C[C@@H]1CCC[C@@H]12.Cl

PYPPENBDXAWXJC-QNTKWALQSA-N

InChI=1S/C15H20N2.ClH/c1-3-11-9-16-7-8-17-10-12-4-2-5-13(12)14(6-1)15(11)17;/h1,3,6,12-13,16H,2,4-5,7-10H2;1H/t12-,13-;/m0./s1

(12R,16S)-7,10-diazatetracyclo[8.6.1.05,17.012,16]heptadeca-1,3,5(17)-triene;hydrochloride

2934.99.9001

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)

DMSO : ~60 mg/mL (~226.59 mM)
H2O : ~4 mg/mL (~15.11 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.44 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 25.0 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: ≥ 2.5 mg/mL (9.44 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 25.0 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: ≥ 2.5 mg/mL (9.44 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 5 mg/mL (18.88 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.)