Guvacine
(Synonyms: 去甲槟榔次碱) 目录号 : GC60890
An inhibitor of GABA uptake
Cas No.:498-96-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Guvacine is an amino acid found in A. catechu (Betel nut).1 It competitively inhibits GABA uptake (IC50 = 10 μM; Ki = 14 μM) in rat hippocampal brain slices.1,2 In vivo, guvacine, at doses ranging from 50-100 mg/kg, decreases spontaneous activity in mice.1 Administration of guvacine also decreases tail flick reaction time in a rat model of morphine analgesia.3
1.Johnston, G.A., Krogsgaard-Larsen, P., and Stephanson, A.Betel nut constituents as inhibitors of γ-aminobutyric acid uptakeNature258(5536)627-628(1975) 2.Pavia, M.R., Lobbestael, S.J., Nugiel, D., et al.Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptakeJ. Med. Chem.35(22)4238-4248(1992) 3.Mantegazza, P., Tammiso, R., Vicentini, L., et al.Nipecotic acid and guvacine antagonism on morphine analgesia in ratsPharmacol. Res. Commun.11(8)657-662(1979)
| Cas No. | 498-96-4 | SDF | |
| 别名 | 去甲槟榔次碱 | ||
| Canonical SMILES | O=C(C1=CCCNC1)O | ||
| 分子式 | C6H9NO2 | 分子量 | 127.14 |
| 溶解度 | 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 | 7.8653 mL | 39.3267 mL | 78.6535 mL |
| 5 mM | 1.5731 mL | 7.8653 mL | 15.7307 mL |
| 10 mM | 0.7865 mL | 3.9327 mL | 7.8653 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。
Catalytic Enantioselective Synthesis of Guvacine Derivatives through [4 + 2] Annulations of Imines with α-Methylallenoates
Org Lett 2018 Oct 5;20(19):6089-6093.PMID:30246538DOI:10.1021/acs.orglett.8b02489.
P-Chiral [2.2.1] bicyclic phosphines (HypPhos catalysts) have been applied to reactions between α-alkylallenoates and imines, producing Guvacine derivatives. These HypPhos catalysts were assembled from trans-4-hydroxyproline, with the modular nature of the synthesis allowing variations of the exocyclic P and N substituents. Among them, exo-( p-anisyl)-HypPhos was most efficacious for [4 + 2] annulations between ethyl α-methylallenoate and imines. Through this method, ( R)-aplexone was identified as being responsible for the decrease in the cellular levels of cholesterol.
Synthesis and Biological Evaluation of Nipecotic Acid and Guvacine Derived 1,3-Disubstituted Allenes as Inhibitors of Murine GABA Transporter mGAT1
ChemMedChem 2019 Jun 18;14(12):1135-1151.PMID:30957949DOI:10.1002/cmdc.201900170.
A new class of nipecotic acid and Guvacine derivatives has been synthesized and characterized for their inhibitory potency at mGAT1-4 and binding affinity for mGAT1. Compounds of the described class are defined by a four-carbon-atom allenyl spacer connecting the nitrogen atom of the nipecotic acid or Guvacine head with an aromatic residue. Among the compounds investigated, the mixture of nipecotic acid derivatives rac-{(Ra )-1-[4-([1,1':2',1''-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} and rac-{(Sa )-1-[4-([1,1':2',1''-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} (21 p), possessing an o-terphenyl residue, was identified as highly selective and the most potent mGAT1 inhibitor in this study. For the (R)-nipecotic acid derived form of 21 p, the inhibitory potency in [3 H]GABA uptake assays was determined as pIC50 =6.78±0.08, and the binding affinity in MS Binding Assays as pKi =7.10±0.12. The synthesis of the designed compounds was carried out by a two-step procedure, generating the allene moiety via allenylation of terminal alkynes which allows broad variation of the terminal phenyl and biphenyl subunit.
Effects of the Areca nut constituents arecaidine and Guvacine on the action of GABA in the cat central nervous system
Brain Res 1977 Nov 18;136(3):513-22.PMID:922499DOI:10.1016/0006-8993(77)90075-0.
Arecaidine and Guvacine, constituents of the nut of Areca catechu, inhibited the uptake of GABA and beta-alanine, but not that of glycine, by slices of cat spinal cord. In cats anesthetised with pentobarbitone, electrophoretic arecaidine enhanced the inhibitory actions of GABA and beta-alanine, but not those of glycine or taurine, on the firing of spinal neurones. Similarly, electrophoretic Guvacine enhanced the inhibition of spinal neurones by GABA but not that by glycine. The uptake of GABA by slices of cat cerebellum was inhibited by arecaidine, and the effect of electrophoretic GABA on the firing of cerebellar Purkinje cells was enhanced by electrophoretic arecaidine. When administered intravenously arecaidine failed to affect synaptic inhibitions considered to be mediated by GABA. Intravenous arecaidine had no effect on either spinal prolonged (presynaptic) inhibition (20mg/kg), dorsal root potentials (20mg/kg) or basket cell inhibition of Purkinje cells (250 mg/kg), although topical arecaidine (6.6-10 x 10(-3) M) blocked this latter inhibition. Large doses of arecaidine (1 g/kg subcutaneous) marginally reduced the lethal effects of bicuculline in mice but appeared to have little or no anticonvulsant activity.
Structure-activity studies on benzhydrol-containing nipecotic acid and Guvacine derivatives as potent, orally-active inhibitors of GABA uptake
J Med Chem 1992 Oct 30;35(22):4238-48.PMID:1433224DOI:10.1021/jm00100a032.
The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and Guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of < 1 microM (including 5, Table I; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.
Kinetic characterization of inhibition of gamma-aminobutyric acid uptake into cultured neurons and astrocytes by 4,4-diphenyl-3-butenyl derivatives of nipecotic acid and Guvacine
J Neurochem 1988 Mar;50(3):818-23.PMID:3339356DOI:10.1111/j.1471-4159.1988.tb02986.x.
The effects of N-(4,4-diphenyl-3-butenyl) derivatives of nipecotic acid (SKF-89976-A and SKF-100844-A) and Guvacine (SKF-100330-A) on neuronal and astroglial gamma-aminobutyric acid (GABA) uptake were investigated. In addition, the uptake of SKF-89976-A was studied using the tritiated compound. All of the compounds were found to be competitive inhibitors of GABA uptake irrespective of the cell type, with Ki values similar to or lower than those of the parent amino acids. Moreover, none of the compounds exhibited selectivity with regard to inhibition of neuronal and glial GABA uptake. In spite of the competitive nature of SKF-89976-A, the compound was not transported by the GABA carriers in the two cell types, because no saturable uptake could be demonstrated.