TPMPA (hydrate)
目录号 : GC48191选择性 GABA\u003csub\u003eA\u003c/sub\u003e-ρ1 (ρ1 GABA\u003csub\u003eC\u003c/sub\u003e) 受体拮抗剂
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
TPMPA is a GABAA-Ρ1 (Ρ1 GABAC) receptor antagonist that is 8-fold selective for GABAA-Ρ1 over GABAA-Ρ2 (Ρ2 GABAC) receptors expressed in X. laevis oocytes (Kbs = 2 and 16 μM, respectively).1 In rat hippocampal slices, TPMPA blocks the inhibitory effect of the GABAB agonist 3-APMPA on excitatory postsynaptic currents (EPSCs) with an EC50 value of 490 μM.2 TPMPA (100 μM) increases light sensitivity and the maximal response of rat retinal ganglion cells without altering their dynamic range.3 In sleeping rats, TPMPA (50 μg, i.c.v.) increases waking from 45 to 62% compared to a vehicle control and decreases slow-wave and paradoxical sleep (REM) by 11 and 5.4%, respectively.4
1.Chebib, M., Mewett, K.N., and Johnston, G.A.GABAC receptor antagonists differentiate between human Ρ1 and Ρ2 receptors expressed in Xenopus oocytesEur. J. Pharmacol.357(2-3)227-234(1998) 2.Ragozzino, D., Woodward, R.M., Murata, Y., et al.Design and in vitro pharmacology of a selective γ-aminobutyric acidC receptor antagonistMol. Pharmacol.50(4)1024-1030(1996) 3.Jensen, R.J.Blocking GABAC receptors increases light responsiveness of retinal ganglion cells in a rat model of retinitis pigmentosaExp. Eye Res.10521-26(2012) 4.Arnaud, C., Gauthier, P., and Gottesmann, C.Study of a GABAC receptor antagonist on sleep-waking behavior in ratsPsychopharmacology (Berl)154(4)415-419(2001)
| Cas No. | N/A | SDF | |
| 化学名 | P-methyl-P-(1,2,3,6-tetrahydro-4-pyridinyl)-phosphinic acid, hydrate | ||
| Canonical SMILES | CP(C1=CCNCC1)(O)=O.O | ||
| 分子式 | C6H12NO2P.XH2O | 分子量 | 161.1 |
| 溶解度 | PBS (pH 7.2): 10 mg/ml | 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 | 6.2073 mL | 31.0366 mL | 62.0732 mL |
| 5 mM | 1.2415 mL | 6.2073 mL | 12.4146 mL |
| 10 mM | 0.6207 mL | 3.1037 mL | 6.2073 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。
Menthol enhances phasic and tonic GABAA receptor-mediated currents in midbrain periaqueductal grey neurons
Br J Pharmacol 2014 Jun;171(11):2803-13.PMID:24460753DOI:10.1111/bph.12602.
Background and purpose: Menthol, a naturally occurring compound in the essential oil of mint leaves, is used for its medicinal, sensory and fragrant properties. Menthol acts via transient receptor potential (TRPM8 and TRPA1) channels and as a positive allosteric modulator of recombinant GABAA receptors. Here, we examined the actions of menthol on GABAA receptor-mediated currents in intact midbrain slices. Experimental approach: Whole-cell voltage-clamp recordings were made from periaqueductal grey (PAG) neurons in midbrain slices from rats to determine the effects of menthol on GABAA receptor-mediated phasic IPSCs and tonic currents. Key results: Menthol (150-750 μM) produced a concentration-dependent prolongation of spontaneous GABAA receptor-mediated IPSCs, but not non-NMDA receptor-mediated EPSCs throughout the PAG. Menthol actions were unaffected by TRPM8 and TRPA1 antagonists, tetrodotoxin and the benzodiazepine antagonist, flumazenil. Menthol also enhanced a tonic current, which was sensitive to the GABAA receptor antagonists, picrotoxin (100 μM), bicuculline (30 μM) and Zn(2+) (100 μM), but unaffected by gabazine (10 μM) and a GABAC receptor antagonist, 1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA; 50 μM). In addition, menthol potentiated currents induced by the extrasynaptic GABAA receptor agonist THIP/gaboxadol (10 μM). Conclusions and implications: These results suggest that menthol positively modulates both synaptic and extrasynaptic populations of GABAA receptors in native PAG neurons. The development of agents that potentiate GABAA -mediated tonic currents and phasic IPSCs in a manner similar to menthol could provide a basis for novel GABAA -related pharmacotherapies.
Functional evidence for different roles of GABAA and GABAB receptors in modulating mouse gastric tone
Neuropharmacology 2010 Jun;58(7):1033-7.PMID:20080114DOI:10.1016/j.neuropharm.2010.01.004.
The aims of the present study were to investigate, using mouse whole stomach in vitro, the effects of gamma-aminobutyric acid (GABA) and GABA receptor agonists on the spontaneous gastric tone, to examine the subtypes of GABA receptors involved in the responses and to determine the possible site(s) of action. GABA induced gastric relaxation, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by phaclofen, GABA(B)-receptor antagonist, but not affected by 1,2,5,6-Tetrahydropyridin-4-yl methylphosphinic acid hydrate (TPMPA), GABA(C)-receptor antagonist. Muscimol, GABA(A)-receptor agonist, mimicked GABA effects inducing relaxation, which was significantly reduced by bicuculline, N omega-nitro-L-arginine methyl ester (L-NAME), inhibitor of NO synthase or apamin, inhibitor of small conductance Ca(2+)-dependent K(+) channels, which blocks the purinergic transmission in this preparation. It was abolished by tetrodotoxin (TTX) or l-NAME plus apamin. Baclofen, a specific GABA(B)-receptor agonist, induced an increase in the gastric tone, which was antagonized by phaclofen and abolished by TTX or atropine. Bicuculline, but not phaclofen or TPMPA, per se induced an increase in gastric tone, which was prevented by L-NAME. In conclusion, our results suggest that GABA is involved in the regulation of mouse gastric tone, through modulation of intrinsic neurons. Activation of GABA(A)-receptors mediates relaxation through neural release of NO and neurotransmitters, activating Ca(2+)-dependent K(+) channels, likely purines, while activation of GABA(B)-receptors leads to contraction through acetylcholine release.
Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: role of GABA(A) and GABA(C) receptors
Neuropharmacology 2007 Jun;52(8):1685-90.PMID:17517423DOI:10.1016/j.neuropharm.2007.03.016.
We investigated, in vitro, the effects of gamma-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C) receptor agonist, induced an inhibitory effect, consisting in the reduction of the amplitude of the spontaneous contractions and muscular relaxation, which was antagonised by TPMPA, GABA(C)-receptor antagonist, TTX or N(omega)-nitro-l-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor, but not affected by hexamethonium. In conclusion, our study indicates that GABA is a modulator of mechanical activity of longitudinal muscle in mouse duodenum. GABA may act through neuronal presynaptic receptors, namely GABA(A) receptors, leading to the release of ACh from excitatory cholinergic neurons, and GABA(C) receptors increasing the release of NO from non-adrenergic, non-cholinergic inhibitory neurons.