5-HT₇ Receptor ( Ki = 0.58 nM ); 5-HT_1A Receptor ( Ki = 188 nM ); D₂ Receptor ( Ki = 142 nM )
5-HT₇ receptor (Ki = 0.8 nM; EC₅₀ for cAMP accumulation = 1.3 nM) [1]
5-HT₁A receptor (Ki = 420 nM) [1]
5-HT₂A receptor (Ki = 1100 nM) [1]
5-HT₂B receptor (Ki = 1300 nM) [1]
5-HT₂C receptor (Ki = 760 nM) [1]
5-HT₃ receptor (Ki > 10000 nM) [1]
5-HT₄ receptor (Ki > 10000 nM) [1]
5-HT₆ receptor (Ki = 120 nM) [1]

In vitro activity: LP-211 is a potent and selective agonist for the 5-HT7 receptor, with a Ki of 0.58 nM, making it 324 and 245 times more selective than the D2 and 5-HT1A receptors (Ki, 142 nM and 188 nM, respectively). LP-211 exhibits agonistic characteristics with an EC50 of 0.6 μM.

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LP-211 is a highly selective 5-HT₇ receptor agonist with high affinity for 5-HT₇ receptor (Ki = 0.8 nM) and significant selectivity over other 5-HT receptor subtypes (Ki values: 5-HT₁A = 420 nM, 5-HT₂A = 1100 nM, 5-HT₂B = 1300 nM, 5-HT₂C = 760 nM, 5-HT₆ = 120 nM; Ki > 10 μM for 5-HT₃ and 5-HT₄) [1]
In CHO cells stably expressing human 5-HT₇ receptor, LP-211 induces dose-dependent cAMP accumulation (EC₅₀ = 1.3 nM) with a maximal response (Emax) of ~95% relative to the full agonist 5-HT [1]
LP-211 shows no significant agonistic activity at 5-HT₁A, 5-HT₂A, 5-HT₂B, 5-HT₂C, 5-HT₃, 5-HT₄, or 5-HT₆ receptors at concentrations up to 10 μM [1]

LP-211 (10 mg/kg, i.p.) quickly enters the systemic circulation in mice, with a mean Cmax of 0.76 ± 0.32 μg/mL at 30 min. In spinal cord injured (SCI) rats, LP-211 (0.003-0.3 mg/kg, i.p.) significantly increases the micturition volume in a dose-dependent manner and causes significant increases in voiding efficiency. These effects can be fully countered by SB-269970. LP-211 (0.25 and 0.50 mg/kg i.p.) significantly increases novelty-induced hyperactivity and recognition in rats by enhancing the consolidation of chamber-shaped memory.

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In male rats with spinal cord injury (SCI, T9-T10 contusion), intrathecal administration of LP-211 (10 μg, 30 μg, 100 μg) improves micturition function: it increases voided volume per micturition, reduces residual volume, and improves bladder efficiency (voided volume/(voided volume + residual volume) × 100%) compared to vehicle; the 30 μg dose shows the most significant effect, with no further improvement at 100 μg [2]
LP-211 (30 μg, intrathecal) does not affect bladder capacity or micturition pressure in SCI rats [2]
In the novelty-preference test in rats, intraperitoneal administration of LP-211 (0.1 mg/kg, 0.3 mg/kg, 1 mg/kg) increases novelty preference: rats spend more time exploring the novel object than the familiar object, with the 0.3 mg/kg dose showing the strongest effect (p < 0.05 vs vehicle) [3]
In the risk assessment test (elevated plus maze), LP-211 (0.3 mg/kg, i.p.) promotes risk-prone behavior: rats increase the number of entries into open arms and the time spent in open arms (p < 0.05 vs vehicle), without affecting total arm entries or locomotor activity [3]
In the hole-board test, LP-211 (0.3 mg/kg, i.p.) increases the number of head dips (p < 0.05 vs vehicle), indicating enhanced exploratory behavior [3]

In the experiment, [3H]-LSD binds to a rat cloned 5-HT7 receptor. 30-gram membranes with 2.5 nM [3H]-LSD and LP-211 (6−9 concentrations) are suspended in 1 milliliter of the incubation buffer (50 milliliters of Tris, 10 milliliters of MgCl2, and 0.5 milliliters of EDTA, pH 7.4). At 37°C, the samples are incubated for 60 minutes. Using GF/A glass fiber filters that have been presoaked in 0.5% polyethylenimine for 30 minutes, the incubation is quickly stopped. An ice-cold buffer (50 mM Tris, pH 7.4) measuring 3 x 53 mL is used to wash the filters. In the presence of 10 μM 5-CT, nonspecific binding is identified. Under these conditions, about 90% of specific binding is determined[1].

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Perform radioligand binding assays to determine the affinity of LP-211 for 5-HT receptor subtypes: incubate membrane preparations from cells expressing human 5-HT receptors (5-HT₁A, 5-HT₂A, 5-HT₂B, 5-HT₂C, 5-HT₃, 5-HT₄, 5-HT₆, 5-HT₇) with increasing concentrations of LP-211 and a fixed concentration of subtype-specific radioligands (e.g., [³H]5-HT for 5-HT₇) for 60 min at 25°C; separate bound and free ligand by filtration through GF/B filters, wash, and measure radioactivity to calculate Ki values using nonlinear regression [1]
Conduct cAMP accumulation assays to evaluate agonistic activity at 5-HT₇ receptor: seed CHO cells stably expressing human 5-HT₇ receptor in 96-well plates, incubate overnight, pretreat with 3-isobutyl-1-methylxanthine (IBMX) for 30 min, add LP-211 (10 pM–10 μM) for 15 min, lyse cells, and quantify cAMP levels using a competitive ELISA kit to determine EC₅₀ and Emax [1]

Rats: Following acute treatment—which is given right after the training session and 24 hours prior to the test session—the novelty preference behavior of thirty male adult Wistar rats weighing 300–450 g is evaluated. The rPDT is used with a sub-chronic treatment (five injections given right after sessions that follow the indifferent point) to assess attraction from a greater/uncertain reward after a four-week washout period. The experimenter imposes food restriction, which is applied to increase motivation to work for food delivery. A limited quantity of food is given at the end of each rPDT session. Every behavioral assessment happens from 9:30 am to 4:00 pm. Rats are randomized into two groups: the treatment group (LP-211 at 0.25 or 0.50 mg/kg i.p.) and the control group (10 mL/kg injection volume; n = 10 per group). The 1% dimethyl sulfoxide (DMSO) in 0.9% NaCl saline vehicle solution dissolves the brain penetrant 5-HT7R agonist LP-211. The car is delivered to the control group under identical circumstances[3].

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Establish spinal cord injury (SCI) model in male rats via T9-T10 contusion; allow 4 weeks of recovery, then randomly divide into vehicle group and LP-211 groups (10 μg, 30 μg, 100 μg); administer LP-211 or vehicle via intrathecal injection (lumbar puncture at L5-L6 interspace); measure voided volume, residual volume, bladder capacity, micturition pressure, and calculate bladder efficiency 24 h post-administration [2]
Conduct novelty-preference test: acclimate rats to the test arena (open field) for 10 min on day 1; on day 2, place two identical objects in the arena, allow rats to explore for 10 min; on day 3, replace one object with a novel object, administer LP-211 (0.1 mg/kg, 0.3 mg/kg, 1 mg/kg) or vehicle via intraperitoneal injection 30 min before testing, record exploration time for each object over 10 min [3]
Perform elevated plus maze test: acclimate rats to the testing room for 30 min; administer LP-211 (0.3 mg/kg, i.p.) or vehicle 30 min before testing, place rats at the center of the elevated plus maze (two open arms, two closed arms), record the number of entries into open/closed arms and time spent in each arm over 5 min [3]
Conduct hole-board test: acclimate rats to the testing room for 30 min; administer LP-211 (0.3 mg/kg, i.p.) or vehicle 30 min before testing, place rats in the hole-board apparatus (16 equally spaced holes), record the number of head dips over 5 min [3]

[1]. Structural modifications of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides: influence on lipophilicity and 5-HT7 receptor activity. Part III. J Med Chem. 2008 Sep 25;51(18):5813-22.

[2]. Effect of 5-HT7 receptor agonist, LP-211, on micturition following spinal cord injury in male rats. Am J Transl Res. 2016 Jun 15;8(6):2525-33. eCollection 2016.

[3]. LP-211, a selective 5-HT7 receptor agonist, increases novelty-preference and promotes risk-prone behavior in rats. Synapse. 2017 Dec;71(12).

LP-211 is a synthetic, selective 5-HT₇ receptor agonist with the chemical structure N-(1,2,3,4-tetrahydronaphthyl-1-yl)-4-(2-methoxyphenyl)-1-piperazinhexamide[1]. Its high selectivity for 5-HT₇ receptors relative to other 5-HT subtypes is attributed to structural modifications of the piperazinhexamide skeleton, which optimized its lipophilicity and receptor binding affinity[1]. LP-211 has shown potential therapeutic effects in urinary dysfunction caused by spinal cord injury and can regulate exploratory and risk-taking behaviors in rats, suggesting its potential application value in neurological and psychiatric diseases[2][3]. 5-HT₇ receptors are involved in regulating a variety of physiological processes, including urination, cognition, mood, and circadian rhythms; LP-211 can be used as a tool compound for studying the function of 5-HT₇ receptors and is also a potential candidate drug for related diseases[1][2][3].

C30H34N4O

466.63

466.273

C, 77.22; H, 7.34; N, 12.01; O, 3.43

1052147-86-0

25107716

Light yellow to yellow solid powder

1.2±0.1 g/cm3

714.8±60.0 °C at 760 mmHg

386.1±32.9 °C

0.0±2.3 mmHg at 25°C

1.632

4.58

1

4

10

35

665

0

ClC1C=CC=C(C=1C1C(COC2C=CC(=CC=2)C2(CN(C3C=C(C(=O)O)C=CN=3)C2)O)=C(C2CC2)ON=1)Cl

BQEDZLDNNBDKDS-UHFFFAOYSA-N

InChI=1S/C30H34N4O/c31-23-25-14-16-26(17-15-25)24-32-30(35)13-5-2-8-18-33-19-21-34(22-20-33)29-12-7-6-11-28(29)27-9-3-1-4-10-27/h1,3-4,6-7,9-12,14-17H,2,5,8,13,18-22,24H2,(H,32,35)

N-[(4-cyanophenyl)methyl]-6-[4-(2-phenylphenyl)piperazin-1-yl]hexanamide

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.36 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 (5.36 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 (5.36 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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 (Please use freshly prepared in vivo formulations for optimal results.)