Pipequaline (PK-8165)
(Synonyms: 哌夸林,PK-8165) 目录号 : GC30827
A partial agonist of central benzodiazepine receptors
Cas No.:77472-98-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Rats: Pipequaline is dissolved in water to give injection volumes of 2 mL/kg. Rats are injected with 5, 10, and 50 mg/kg pipequaline. Infrared cells in the walls of the box provided automated measures of locomotor activity and rearing, respectively[3]. |
References: [1]. Bradwejn J, et al. Effects of PK 8165, a partial benzodiazepine receptor agonist, on cholecystokinin-inducedactivation of hippocampal pyramidal neurons: a microiontophoretic study in the rat. Eur J Pharmacol. 1985 Jun 19;112(3):415-8. | |
Pipequaline is a partial agonist of central benzodiazepine receptors (Ki = 78 nM in a radioligand binding assay).1 In mice, pipequaline enhances the effects of diazepam , further reducing foot shock-induced fighting behavior and the number of maximal electroshock-induced seizures and potentiating the muscle relaxant and hypnotic effects.2 Pipequaline also increases drinking in the Vogel punished drinking task indicating anxiolytic-like activity that can be reversed by the benzodiazepine receptor antagonist flumazenil .
1.Le Fur, G., Mizoule, J., Burgevin, M.C., et al.Multiple benzodiazepine receptors: Evidence of a dissociation between anticonflict and anticonvulsant properties by PK 8165 and PK 9084 (two quinoline derivatives)Life Sci.28(13)1439-1448(1981) 2.Mizoule, J., Rataud, J., Uzan, A., et al.Pharmacological evidence that PK 8165 behaves as a partial agonist of brain type benzodiazepine receptorsArch. Int. Pharmacodyn. Ther.271(2)189-197(1984)
| Cas No. | 77472-98-1 | SDF | |
| 别名 | 哌夸林,PK-8165 | ||
| Canonical SMILES | C1(C2=CC=CC=C2)=NC3=CC=CC=C3C(CCC4CCNCC4)=C1 | ||
| 分子式 | C22H24N2 | 分子量 | 316.44 |
| 溶解度 | DMSO : ≥ 32 mg/mL (101.13 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1602 mL | 15.8008 mL | 31.6016 mL |
| 5 mM | 0.632 mL | 3.1602 mL | 6.3203 mL |
| 10 mM | 0.316 mL | 1.5801 mL | 3.1602 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Evaluation of the sedative properties of PK 8165 (pipequaline), a benzodiazepine partial agonist, in normal subjects
The sedative properties of two doses (50 and 150 mg) of a benzodiazepine partial agonist, PK 8165 (pipequaline), were compared to diazepam 10 mg and placebo in 12 normal volunteers. The assessment, performed before drug intake and 2 and 5 hours after drug intake, included a battery of visual analogue scales and standardized computerized tests (labyrinths, series of digits, colour test, and Zazzo test). Results showed that, at low dose, PK 8165 is not only devoid of any sedative effect but presents psychostimulating properties. In contrast, diazepam 2 hours after intake and PK 8165 150 mg, 5 hours after drug intake induced a significant decrease in performance compared to placebo. This study suggests that small doses of PK 8165 merits further development as an anxiolytic/psychostimulating drug devoid of sedative properties.
Phenylquinolines PK 8165 and PK 9084 allosterically modulate [35S]t-butylbicyclophosphorothionate binding to a chloride ionophore in rat brain via a novel Ro5 4864 binding site
The binding of the cage convulsant, [35S]t-butylbicyclophosphorothionate ([35S]TBPS), to a picrotoxin-sensitive site in rat cerebral cortical homogenates was used to identify and characterize the site of action of the phenylquinolines PK 8165 and PK 9084, the isoquinoline PK 11195 and the atypical benzodiazepine (BZ) Ro5 4864. These agents were found to allosterically modulate the binding of 2 nM [35S]TBPS in a pharmacologically relevant fashion. Evidence is presented to suggest that these compounds share a common site of action as modulators of [35S]TBPS binding. The relative potencies of these compounds in vitro are in the submicromolar to micromolar concentration range and correlate well with the concentrations reported to elicit specific responses in behavioral and electrophysiologic studies. Modulation of [35S]TBPS binding in vitro is affected by micromolar quantities of gamma-aminobutyric acid in a (+)-bicuculline-sensitive fashion and is unaffected by the central BZ receptor "antagonist" Ro15 1788. Collectively, the evidence presented suggests the existence of a novel drug binding site that is functionally coupled to a gamma-aminobutyric acid-A receptor and a [35S]TBPS-labeled chloride ionophore. Moreover, this site is distinct from the central BZ receptor recognized by clonazepam and the high-affinity peripheral BZ binding site labeled by [3H] Ro5 4864. The hypothesis is proposed that the novel "Ro5 4864 site" identified in the present study is a functionally relevant binding site that mediates some of the pharmacologic effects of Ro5 4864, PK 8165, PK 9084 and PK 11195 in the mammalian central nervous system.
Sedative effects of PK 9084 and PK 8165, alone and in combination with chlordiazepoxide
1 The sedative effects in rats of two phenylquinolines, PK 9084 and PK 8165 (5-50 mg/kg), were examined in a holeboard: both when given alone and when given in conjunction with chlordiazepoxide (5 mg/kg). 2 Both phenylquinolines produced significant dose-related decreases in locomotor activity and rearing, with an ED50 about twice that for chlordiazepoxide. 3 When the phenylquinolines were combined with chlordiazepoxide the degree of sedation was equal to that seen with either drug given alone, whichever produced the greater sedation; the sedative effects of the two drugs were never additive. 4 PK 9084 (10 and 50 mg kg) significantly reduced rectal temperature, as did chlordiazepoxide (5 mg/kg), but there was no addition nor interaction of their effects. 5 Both phenylquinolines also reduced exploratory head-dipping, as did chlordiazepoxide, but in combination they antagonized each other's effects. 6 The classification of the phenylquinolines as non-sedative anxiolytics, acting as agonists at the benzodiazepine receptors needs revision.
The effects of alcohol on psychological functions in normal volunteers after 8 days' treatment with pipequaline (PK 8165), diazepam or placebo
The effects of daily administration for 8 days of 50 mg pipequaline, 10 mg diazepam and placebo were assessed in a double-blind cross-over study with 12 healthy volunteers. This study also tested for an interaction between the drugs and alcohol on the eighth day. Subjective ratings, psychomotor and memory performance were evaluated. Diazepam produced the typical pattern of changes, namely impairments in psychomotor performance and reductions in the retention of newly memorised information. In contrast, the effects of pipequaline were relatively minor. In general, neither drug potentiated the effects of alcohol on performance, only isolated instances of non-additive interactions occurring. Subjective reports revealed that whereas both active drugs increased feelings of calmness, this result was accomplished by pipequaline with considerably less drowsiness, no euphoria and a general absence of the adverse side effects of diazepam.
Behavioural effects of PK 8165 that are not mediated by benzodiazepine binding sites
The phenylquinoline, PK 8165 (5-25 mg/kg), produced dose-related reductions in locomotor activity, rearing and exploratory head-dipping in a holeboard. Neither Ro 15-1788 (1, 10 or 20 mg/kg) nor CGS 8216 (1 or 10 mg/kg) was able to reverse the reductions in locomotor activity or rearing. This suggests that at least some of the behavioural effects of PK 8165 are not mediated by a site on the GABA-benzodiazepine receptor complex. This conclusion is supported by the recent report [9] that, whereas PK 8165 potently displaces benzodiazepines from their binding site in vitro, it is without effect in vivo.