5-HT_2C Receptor ( pEC50 = 9.96 ); 5-HT_2B Receptor ( pEC50 = 7.19 ); 5-HT_2A Receptor ( pEC50 = 6.81 )
5-HT2C receptor (full agonist, EC50 = 0.1 nM in human, 0.06 nM in rat; pEC50 = 9.96 ± 0.11 in FLIPR assay; pKi = 8.80 ± 0.11, Ki = 1.6 nM in binding assay)
5-HT2A receptor (partial agonist, EC50 = 1536 nM in FLIPR assay; pKi = 7.22 ± 0.15, Ki = 6.0 nM in binding assay)
5-HT2B receptor (partial agonist, EC50 = 65.3 nM in FLIPR assay; pKi = 7.19 ± 0.25, Ki = 64 nM in binding assay)
Other receptors with Ki > 1 µM except: human 5-HT3 (Ki = 195 nM), bovine 5-HT1D (Ki = 136 nM), rat 5-HT7 (Ki = 661 nM), human D2 (Ki = 872 nM), human histamine H1 (Ki = 828 nM), human adrenergic alpha1A (Ki = 217 nM), human adrenergic alpha2A (Ki = 956 nM) [1]

CP-809,101 is a potent and functionally selective full agonist at the 5-HT2C receptor, showing >500-fold selectivity over 5-HT2A and 5-HT2B receptors in FLIPR assays. It acts as a partial agonist at 5-HT2A and 5-HT2B receptors with lower potency. Binding assays confirm high affinity for 5-HT2C (Ki = 1.6 nM) and lower affinity for 5-HT2A (Ki = 6.0 nM) and 5-HT2B (Ki = 64 nM). [1]
In GTPγS binding assays, CP-809,101 shows potent agonist activity at human 5-HT2C receptors (pEC50 = 9.08 ± 0.16, EC50 = 0.83 nM, efficacy = 96%). [1]
Calcium mobilization assays demonstrate functional selectivity for 5-HT2C over 5-HT2A and 5-HT2B receptors. [1]

CP-809101 hydrochloride (0.1-56 mg/kg; s.c.; single) suppresses rats' conditioned avoidance response in a dose-dependent manner[1].
CP-809101 hydrochloride (0.56, 1.78, 5.6, 17.8 mg/kg; s.c.; single) inhibits the hyperactivity brought on by d-amphetamine and PCP (phencyclidine hydrochloride), the latter of which is dose-dependent[1].
CP-809101 hydrochloride (0.56, 1.78, 5.6, 17.8 mg/kg; s.c.; single) reduces spontaneous locomotor activity in a dose-dependent manner with an ED50 value of 2.2 mg/kg[1].
CP-809101 hydrochloride (0.3, 1, 3 mg/kg; s.c.; single) inhibits the discriminative stimulus properties of nicotine and decreases responding to both food and nicotine[2].

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CP-809,101 dose-dependently inhibits conditioned avoidance responding (CAR) in rats with an ED50 = 4.8 mg/kg (sc). This effect is completely blocked by the 5-HT2C antagonist SB-224,282. [1]
It antagonizes PCP-induced hyperactivity (ED50 = 2.4 mg/kg) and d-amphetamine-induced hyperactivity (ED50 = 2.9 mg/kg). [1]
CP-809,101 reverses apomorphine-induced deficit in prepulse inhibition (PPI) at 3.2 mg/kg, comparable to haloperidol. [1]
No catalepsy is observed up to 56 mg/kg. [1]
It shows no antidepressant-like activity in forced swim test or learned helplessness models. [1]
Improves cognitive performance in novel object recognition test at 1 mg/kg. [1]

For 5-HT2C receptor binding: Membranes expressing human 5-HT2C receptors are prepared from NIH 3T3 cells. Assay buffer contains 50 mM Tris (pH 7.7), 10 mM MgCl2, 3 mM CaCl2, 1 mM EDTA, 10 µM pargyline, and 0.1% ascorbic acid. [3H]5-HT is used as radioligand. Incubation is at 37°C for 60 min. Non-specific binding is defined with mianserin (10 µM). [1]
For 5-HT2A receptor binding: Similar membrane preparation from cells expressing human 5-HT2A receptors. Assay buffer contains 50 mM HEPES (pH 7.4), 0.5 mM EDTA, 0.5 mM EGTA, 37.5 mM KCl, 2.5 mM MgCl2. Radioligand [125I]DOI is used. Incubation at 37°C for 60 min. Non-specific binding is defined with mianserin (10 µM). [1]

Calcium mobilization assay: Cells expressing 5-HT2C, 5-HT2A, or 5-HT2B receptors are plated in 384-well plates and loaded with Fluo-4 dye. After washing, fluorescence is measured using FLIPR. Compounds are added and calcium response is recorded. [1]
GTPγS binding assay: Membranes from cells expressing 5-HT2C receptors are incubated with test compounds and europium-labeled GTP. Fluorescence is measured after incubation and washing. [1]

Animal/Disease Models: Male CF rat (conditioned avoidance response (CAR) model) [1].
Doses: 0.1-56 mg/kg
Route of Administration: subcutaneous injection; single.
Experimental Results: Dose-dependent inhibition of conditioned avoidance response, with ID50 value of 4.8 mg/kg.

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Animal/Disease Models: Male CD rat (PCP or d-amphetamine-induced hyperactivity model) [1].
Doses: 0.56, 1.78, 5.6, 17.8 mg/kg
Route of Administration: subcutaneous injection; single.
Experimental Results: Antagonizes the hyperactivity caused by PCP, with an ED50 value of 2.4 mg/kg. Antagonizes d-amphetamine-induced ADHD with an ED50 value of 2.7 mg/kg in a dose-dependent manner.

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Animal/Disease Models: Male CD rat (spontaneous movement model) [1].
Doses: 0.56, 1.78, 5.6, 17.8 mg/kg
Route of Administration: subcutaneous injection; single.
Experimental Results: Inhibition of spontaneous locomotor activity in a dose-dependent manner (ED50=2.7 mg/kg).

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Animal/Disease Models: Adult male SD (SD (Sprague-Dawley)) rat (280-400 g) [2].
Doses: 0.3, 1, 3 mg/kg
Route of Administration: subcutaneous injection; single.
Experimental Results: Rats demonstrated dose-r

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Male CF rats (conditioned avoidance responding (CAR) model)
0.1-56 mg/kg
Subcutaneous injection; single.

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Conditioned avoidance responding (CAR): Male CF rats are trained to avoid shock. CP-809,101 is administered subcutaneously 30 min before testing. Vehicle: 5% DMSO, 5% Emulphor, 90% saline or 40% hydroxypropyl-beta-cyclodextrin. [1]
Locomotor activity: Male CD rats are habituated overnight. CP-809,101 is given 60 min before activity measurement in dark cycle. [1]
PCP or amphetamine-induced hyperactivity: Rats are treated with CP-809,101 1 h before PCP (3.2 mg/kg) or d-amphetamine (1 mg/kg). Activity is recorded for 3 h. [1]
Prepulse inhibition: Male Wistar rats receive CP-809,101 30 min before apomorphine (1 mg/kg). Startle response and PPI are measured. [1]
Catalepsy: Rats are placed with forepaws on a bar; latency to move is recorded up to 90 s. [1]
Forced swim test: Mice are placed in water for 7 min after drug administration (60 min pretreatment). Immobility is scored. [1]
Learned helplessness: Mice receive inescapable shock on days 1–2, then avoidance testing on day 4 after drug treatment. [1]
Novel object recognition: Mice are habituated, then exposed to objects after drug administration (30 min pretreatment). Exploration time is recorded. [1]

[1]. CP-809,101, a selective 5-HT2C agonist, shows activity in animal models of antipsychotic activity. Neuropharmacology. 2007 Feb;52(2):279-90.

[2]. Evaluation of chemically diverse 5-HT₂c receptor agonists on behaviours motivated by food and nicotine and on side effect profiles. Psychopharmacology (Berl). 2013 Apr;226(3):475-90.

CP-809,101 is a potent, functionally selective 5-HT(2C) receptor agonist with near-100% efficacy in vitro. This study aimed to evaluate the efficacy of this selective 5-HT(2C) receptor agonist in an animal model predicting the efficacy and risk of side effects of antipsychotic drugs. Similar to existing antipsychotics, CP-809,101 dose-dependently inhibits conditioned avoidance response (CAR, ED(50) = 4.8 mg/kg, subcutaneous injection). Concomitant administration of the 5-HT(2C) receptor antagonist SB-224,282 completely antagonized the inhibitory effect of CP-809,101 on CAR. CP-809,101 antagonized PCP- and d-amphetamine-induced hyperactivity with ED50 values of 2.4 and 2.9 mg/kg (subcutaneous injection), respectively, and also reversed apomorphine-induced prepulse inhibition defects. At doses up to 56 mg/kg, CP-809,101 did not induce rigidity. Therefore, the results of this study indicate that the pharmacological properties of the 5-HT2C receptor agonist CP-809,101 are similar to those of atypical antipsychotics with a low incidence of extrapyramidal symptoms. CP-809,101 was inactive in two animal models of antidepressant-like activity (forced swimming test and learned helplessness model). However, CP-809,101 showed activity in novel object recognition (an animal model of cognitive function). These data suggest that 5-HT(2C) agonists may be a novel approach for treating psychosis and improving cognitive impairment associated with schizophrenia. [1]

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Selective 5-HT2C receptor agonists, such as lorcaserin, are being developed for the treatment of obesity. Studies have shown that they may also have the potential to treat addictive behaviors, including nicotine dependence, although the number of such drugs evaluated is small. Objective: The primary objective was to evaluate the effects of the highly selective 5-HT2C agonist CP-809101 on food-motivated behaviors (operational FR5 and progressive ratio reinforcement programs, palatability-induced feeding) and nicotine-motivated behaviors (intravenous self-administration, drug discrimination) in rats, and to compare these effects with those of the structurally different 5-HT2C receptor agonists lorcaserin and Ro 60-0175. Secondary objectives were to assess the side effect profiles of lorcaserin and CP-809101 and to determine the plasma concentrations of lorcaserin at doses (1 mg/kg) that reduce food and nicotine fortification, for comparison with plasma concentrations reported in human trials. Results: CP-809101 (0.3–3 mg/kg subcutaneously) reduced responses to nicotine and food and blocked the discriminative stimuli of nicotine in a manner similar to that of lorcaserin and Ro 60-0175. Following administration of high doses of CP-809101 and lorcaserin, behaviors such as decreased activity, chewing, and ptosis were observed. Plasma concentrations of lorcaserin were similar to those reported in obesity trials. Conclusion: These studies support the use of 5-HT2C receptor agonists as a treatment for nicotine dependence. Plasma exposure levels following acute lorcaserin treatment suggest that equivalent doses can be used to assess the efficacy of these drugs in obesity and smoking cessation trials. Finally, the side effect profiles of lorcaserin and CP-809101 may differ, suggesting that tolerability to 5-HT2C receptor agonists may vary. [2]

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CP-809,101 is a novel selective 5-HT2C receptor agonist with antipsychotic-like activity in animal models, low incidence of extrapyramidal symptoms, and potential cognitive enhancement. [1]
It may represent a new approach to treating psychotic symptoms and cognitive impairment in patients with schizophrenia. [1]

C15H18CL2N4O

341.2356

340.086

C, 52.80; H, 5.32; Cl, 20.78; N, 16.42; O, 4.69

1215721-40-6

CP-809101; 479683-64-2

56972220

Light yellow to yellow solid powder

3.314

2

5

4

22

314

0

ClC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])OC1C([H])=NC([H])=C(N=1)N1C([H])([H])C([H])([H])N([H])C([H])([H])C1([H])[H].Cl[H]

NMUNRTCTDLORDR-UHFFFAOYSA-N

InChI=1S/C15H17ClN4O.ClH/c16-13-3-1-2-12(8-13)11-21-15-10-18-9-14(19-15)20-6-4-17-5-7-20;/h1-3,8-10,17H,4-7,11H2;1H

2-[(3-chlorophenyl)methoxy]-6-piperazin-1-ylpyrazine;hydrochloride

CP809101 HCl; CP809101; CP 809101; CP 809101 hydrochloride; CP-809101 hydrochloride; CP-809101 (hydrochloride); 2-[(3-CHLOROPHENYL)METHOXY]-6-(1-PIPERAZINYL)PYRAZINE HYDROCHLORIDE; CP-809101 HCl; 2-((3-Chlorobenzyl)oxy)-6-(piperazin-1-yl)pyrazine hydrochloride; 2-[(3-chlorophenyl)methoxy]-6-piperazin-1-ylpyrazine;hydrochloride; CP-809101

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)

H2O: ~20 mg/mL (~58.6 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.)