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Purity: ≥98%
Pipequaline (also known as PK-8165; PK 8165), a quinoline derivative and a ligand of the benzodiazepine binding site, is a clinically-effective anxiolytic, which is devoid of sedative and anticonvulsant properties, but it was never marketed. It is a partial benzodiazepine receptor agonist with anxiolytic activity and possesses a novel chemical structure that is not closely related to other drugs of this type. TPK 8165, applied microiontophoretically or administered i.v. at low doses, suppressed CCK-8S-induced activation of hippocampal pyramidal neurons, whereas, at high doses it antagonized the effect of microiontophoretic applications of flurazepam. These results indicate that PK 8165 acts as a mixed agonist-antagonist at BZD receptors and suggest that the suppression of CCK-8S-induced activation by BZD might be related to their anxiolytic property rather than to their sedative or anticonvulsant activity.
| Targets |
Benzodiazepine (BZD) receptors (neuronal type) [1]
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| ln Vitro |
Microiontophoretic application of PK 8165 (25 mM, pH 7) selectively reversed the activation of CA₁ and CA₃ hippocampal pyramidal neurons induced by cholecystokinin-8S (CCK-8S), but did not affect activation induced by acetylcholine or [Met⁵]enkephalin. [1]
- The effect of microiontophoretically applied PK 8165 on CCK-8S-induced activation was completely blocked by the BZD antagonist RO 15-1788 (3.5 mg/kg i.v.). [1] |
| ln Vivo |
The activation of kainate, glutamate, and acetylcholine was partially suppressed by piperaquinoline administered intravenously. Piperaquinoline microiontophoresis decreases kainic acid-induced neuronal activity [2]. Locomotor activity is reduced in a dose-related manner by piperaquinoline. In a dose-related way, piperaquinoline dramatically lowers the frequency of head bowing episodes [3].
Intravenous administration of low doses (100–500 µg/kg) of PK 8165 selectively reduced CCK-8S-induced activation of hippocampal pyramidal neurons without affecting responses to acetylcholine or [Met⁵]enkephalin. The ED₅₀ for this effect was 313 ± 43.2 µg/kg (mean ± S.E.). [1] - At high doses (>600 µg/kg i.v.), PK 8165 did not suppress CCK-8S-induced activation and instead antagonized the suppressive effect of microiontophoretically applied flurazepam on such activation. High doses also antagonized the effect of microiontophoretically applied PK 8165 itself. [1] - PK 8165 exhibits anxiolytic activity in experimental animals without sedative or anticonvulsant effects at doses producing anticonflict effects. [1] |
| Animal Protocol |
Adult male Sprague-Dawley rats (200–300 g) were anesthetized with urethane (1.25 g/kg i.p.). A five-barreled micropipette was used for extracellular recording from pyramidal neurons in the CA₁ and CA₃ regions of the dorsal hippocampus. The central barrel was filled with 2 M NaCl and a dye for recording and marking sites. Side barrels were used for microiontophoretic application of substances: CCK-8S (10 µM in 0.2 M NaCl, pH 5), acetylcholine chloride (20 mM, pH 4), flurazepam-HCl (20 mM, pH 4), [Met⁵]enkephalin (0.5 mM in 0.2 M NaCl with 0.01% bovine serum albumin, pH 4.6), and PK 8165 (25 mM, pH 7). Pyramidal cells were identified by action potential characteristics. For intravenous administration, PK 8165 was dissolved and injected at doses ranging from 100 to >600 µg/kg. Recording sites were marked by ejecting dye with a -27 µA current for 20 minutes, followed by histological verification. [1]
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| ADME/Pharmacokinetics |
PK 8165 has a very short half-life in rats. The effect of intravenous injection of PK 8165 on benzodiazepine receptor-mediated responses is short-lived (completely recovered within 20 minutes after injection). [1]
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| Toxicity/Toxicokinetics |
At doses that produce anxiolytic (anti-conflict) effects, PK 8165 does not impair motor activity and has no sedative or anticonvulsant effects. [1]
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| References |
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| Additional Infomation |
Pipequaline is a quinoline derivative that is both anti-conflict and anticonvulsant. It is an anti-anxiety drug that has never been marketed. Its unique chemical structure is different from that of other drugs in its class. The pharmacological properties of Pipequaline are similar to those of benzodiazepines that have been reported. However, it has significant anxiolytic effects, while its sedative, amnesic, or anticonvulsant effects are weak. Due to these differences, the drug is classified as a non-benzodiazepine anxiolytic.
PK 8165 (a phenylquinoline derivative) is a partial agonist of benzodiazepine receptors. It binds selectively to neuronal benzodiazepine receptors with high affinity, while its affinity for peripheral receptors is much lower. [1] - At low doses, the ability of PK 8165 to inhibit CCK-8S-induced hippocampal neuronal activation is considered a potential electrophysiological factor related to its anxiolytic effects, which are similar to those of benzodiazepines but different from their sedative and anticonvulsant effects. [1] - Early clinical trials have shown that PK 8165 is an effective anxiolytic with no sedative effect. [1] |
| Molecular Formula |
C22H24N2
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|---|---|
| Molecular Weight |
316.4394
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| Exact Mass |
316.194
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| CAS # |
77472-98-1
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| Related CAS # |
Pipequaline hydrochloride;80221-58-5
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| PubChem CID |
71219
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| Appearance |
White to off-white solid powder
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| Density |
1.078g/cm3
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| Boiling Point |
489.2ºC at 760 mmHg
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| Flash Point |
249.7ºC
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| Index of Refraction |
1.602
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| LogP |
5.162
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
370
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AMEWZCMTSIONOX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24N2/c1-2-6-18(7-3-1)22-16-19(11-10-17-12-14-23-15-13-17)20-8-4-5-9-21(20)24-22/h1-9,16-17,23H,10-15H2
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| Chemical Name |
2-Phenyl-4-(2-(4-piperidyl)ethyl)quinoline
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| Synonyms |
PK 8165; PK-8165; PK8165.
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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 |
| 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) |
DMSO : ≥ 32 mg/mL (~101.13 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1602 mL | 15.8008 mL | 31.6016 mL | |
| 5 mM | 0.6320 mL | 3.1602 mL | 6.3203 mL | |
| 10 mM | 0.3160 mL | 1.5801 mL | 3.1602 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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