| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Penfluridol (formerly TLP-607; McN-JR-16341; R-16341; Acemap; Semap) is a 1st generation, long-acting and diphenylbutylpiperidine-based antipsychotic medication used for maintenance/long-term treatment of schizophrenia or other psychotic disorders.
| Targets |
Dopamine receptor ( Ki = 1.6 μM )
Dopamine D2 receptor (Ki = 0.8 nM) [2] |
|---|---|
| ln Vitro |
In vitro activity: Penfluridol is a long-acting neuroleptic medication that can treat both positive and negative symptoms of schizophrenia. With a Ki of 1.6 μM, penfluridol prevents dopamine from binding to the dopamine receptor. It works as an antipsychotic by inhibiting dopamine projections in the mesocortical area and limbic system.[1] Penfluridol competitively opposes potassium-induced calcium-dependent contractions in the rat vas deferens and specifically blocks [3H]nitrendipine's binding to the cerebral cortical membrane fraction of the rat. Penfluridol (10 μM) inhibits calcium influx during either NE or KCl stimulation, as well as the contractile response of isolated rings of rabbit thoracic aorta to these stimuli.[2]
Penfluridol (R-16341) exhibited high affinity for dopamine D2 receptors in rat striatal membrane preparations. At 1 nM, it inhibited 70% of [³H]-spiperone binding to D2 receptors, with a Ki value of 0.8 nM [2] - The compound showed no significant binding to dopamine D1 receptors, serotonin 5-HT2 receptors, or α-adrenergic receptors at concentrations up to 100 nM [2] |
| ln Vivo |
In mice treated with amphetamine (5 mg/kg, i.p.) to induce hyperlocomotion, oral administration of Penfluridol (0.5, 1, 2 mg/kg) dose-dependently reduced locomotor activity. The 2 mg/kg dose inhibited hyperlocomotion by 80% compared to the control group, with a duration of action exceeding 24 hours [1]
- In rats with reserpine-induced catalepsy, Penfluridol (1 mg/kg, p.o.) reversed catalepsy scores by 60% within 4 hours of administration, via D2 receptor antagonism [1] |
| Enzyme Assay |
Rat striatal membranes were prepared and suspended in assay buffer. Serial dilutions of Penfluridol (0.01–100 nM) were mixed with membrane suspensions and [³H]-spiperone (a selective D2 receptor ligand). The mixture was incubated at 37°C for 60 minutes, unbound ligands were removed by filtration through glass fiber filters, and radioactivity was measured. Ki values were calculated using the Cheng-Prusoff equation [2]
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| Cell Assay |
Cell Line: Human AML cell lines, HL-60 (FLT3-WT), U937 (FLT3-WT), and MV4–11 (FLT3-ITD)
Concentration: 1.25, 2.5, 5, 10, 20, 40 μM Incubation Time: 24, 48 h Result: Significantly reduced cell viability in a concentration-dependent manner. |
| Animal Protocol |
DBA/1J male mice aged 10–12 weeks with type II chicken collagen-induced arthritis (CIA) model
10 mg/kg Daily oral gavage; from the 18th day after the first immunization Mouse Amphetamine-Induced Hyperlocomotion Model: Male ICR mice were randomly divided into control (saline) and Penfluridol groups (0.5, 1, 2 mg/kg, p.o., n=6 per group). Drugs were administered 60 minutes before amphetamine (5 mg/kg, i.p.). Locomotor activity was recorded for 120 minutes using an automated activity monitor [1] - Rat Reserpine-Induced Catalepsy Model: Male Wistar rats were injected with reserpine (5 mg/kg, i.p.) to induce catalepsy. Penfluridol (1 mg/kg, p.o.) or saline was administered 2 hours post-reserpine. Catalepsy scores were evaluated every 60 minutes for 6 hours based on the time rats maintained a fixed posture [1] |
| ADME/Pharmacokinetics |
In rats, the oral bioavailability of Penfluridol (2 mg/kg) was 55%, the peak plasma concentration (Cmax) was 22 ng/mL, and the time to peak concentration (Tmax) was 4 hours [2]. The plasma half-life (t1/2) in rats was 36 hours, and the volume of distribution was 18 L/kg. It has a high binding rate to plasma proteins (99%) [2]. The drug is slowly metabolized in the liver, with approximately 40% of the dose excreted in feces within 7 days and 25% in urine, mainly existing as metabolites [2].
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| Toxicity/Toxicokinetics |
The oral LD50 of piperidone was 120 mg/kg in mice and 180 mg/kg in rats [1]
- Mild extrapyramidal symptoms (e.g., tremor, rigidity) were observed in rats at doses ≥5 mg/kg, and these symptoms were reversible [1] - No significant hepatotoxicity or nephrotoxicity was detected in short-term animal studies (14 days), and serum ALT, AST, creatinine, and urea nitrogen levels were all within the normal range [2] |
| References | |
| Additional Infomation |
1-[4,4-bis(4-fluorophenyl)butyl]-4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol is a diarylmethane compound. It is one of the long-acting antipsychotics used for maintenance or long-term treatment of schizophrenia and other mental disorders. Piperidinol (R-16341) is a long-acting diphenylbutylpiperidine antipsychotic [1][2] - Its main mechanism of action is selective antagonism of dopamine D2 receptors in the central nervous system (especially the striatum) [1][2] - Clinical indications include the treatment of schizophrenia, especially for patients with poor compliance, because of its long duration of action [1][2] - Due to its high plasma protein binding and slow metabolism, it has a long duration of action and allows for once-weekly oral administration. Dosage in clinical practice [2]
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| Molecular Formula |
C28H27CLF5NO
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|---|---|---|
| Molecular Weight |
523.97
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| Exact Mass |
523.17
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| Elemental Analysis |
C, 64.18; H, 5.19; Cl, 6.77; F, 18.13; N, 2.67; O, 3.05
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| CAS # |
26864-56-2
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| Related CAS # |
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| PubChem CID |
33630
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
587.7±50.0 °C at 760 mmHg
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| Melting Point |
105-107ºC
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| Flash Point |
309.2±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.553
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| LogP |
6.01
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
647
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1C(F)(F)F)C1(C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])C([H])(C2C([H])=C([H])C(=C([H])C=2[H])F)C2C([H])=C([H])C(=C([H])C=2[H])F)C([H])([H])C1([H])[H])O[H]
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| InChi Key |
MDLAAYDRRZXJIF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H27ClF5NO/c29-26-12-7-21(18-25(26)28(32,33)34)27(36)13-16-35(17-14-27)15-1-2-24(19-3-8-22(30)9-4-19)20-5-10-23(31)11-6-20/h3-12,18,24,36H,1-2,13-17H2
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| Chemical Name |
1-[4,4-bis(4-fluorophenyl)butyl]-4-[4-chloro-3-(trifluoromethyl)phenyl]piperidin-4-ol
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.77 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. Solubility in Formulation 2: 2.5 mg/mL (4.77 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5%DMSO + 5%Tween 80 + 50%ddH2O: 5.0mg/ml (9.54mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9085 mL | 9.5425 mL | 19.0851 mL | |
| 5 mM | 0.3817 mL | 1.9085 mL | 3.8170 mL | |
| 10 mM | 0.1909 mL | 0.9543 mL | 1.9085 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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