Picrotoxinin
(Synonyms: 木防己苦毒宁) 目录号 : GC61186
Picrotoxinin, a potent convulsant, is a chloride channel blocker. Picrotoxinin is a noncompetitive GABAA receptor antagonist, which negatively modulates the action of GABA on GABAAA receptors.
Cas No.:17617-45-7
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
Picrotoxinin, a potent convulsant, is a chloride channel blocker. Picrotoxinin is a noncompetitive GABAA receptor antagonist, which negatively modulates the action of GABA on GABAAA receptors.
| Cas No. | 17617-45-7 | SDF | |
| 别名 | 木防己苦毒宁 | ||
| Canonical SMILES | O=C1[C@]([C@@H]2C(C)=C)([H])[C@]3(O)C[C@]4([H])[C@](O4)(C(O5)=O)[C@]3(C)[C@@]5([H])[C@]2([H])O1 | ||
| 分子式 | C15H16O6 | 分子量 | 292.28 |
| 溶解度 | DMSO : 100 mg/mL (342.14 mM; Need ultrasonic) | 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 | 3.4214 mL | 17.1069 mL | 34.2138 mL |
| 5 mM | 0.6843 mL | 3.4214 mL | 6.8428 mL |
| 10 mM | 0.3421 mL | 1.7107 mL | 3.4214 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。
Revision of the Unstable Picrotoxinin Hydrolysis Product
Angew Chem Int Ed Engl 2021 Aug 23;60(35):19113-19116.PMID:34236745DOI:10.1002/anie.202107785.
The plant metabolite Picrotoxinin (PXN) is a widely used tool in neuroscience for the identification of GABAergic signaling. Its hydrolysis in weakly alkaline media has been observed for over a century and the structure of the unstable hydrolysis intermediate was assigned by analogy to the degradation product picrotoxic acid. Here we show this assignment to be in error and we revise the structure of the hydrolysis product by spectroscopic characterization in situ. Counterintuitively, hydrolysis occurs at a lactone that remains closed in the major isolable degradation product, which accounts for the longstanding mistake in the literature.
The binding mode of Picrotoxinin in GABAA-ρ receptors: Insight into the subunit's selectivity in the transmembrane domain
Comput Biol Chem 2016 Oct;64:202-209.PMID:27423910DOI:10.1016/j.compbiolchem.2016.07.003.
The channel blocker Picrotoxinin has been studied with GABAA-ρ1 and GABAA-ρ2 homology models based on the GluCl crystal structure. Picrotoxinin is tenfold more potent for GABAA-ρ2 than for GABAA-ρ1 homomeric channels. This intra-subunit selectivity arises from the unconserved residues at the 2' sites, which are the essential molecular basis for both the binding and potency of Picrotoxinin. The serine residues at the 2' positions of the ρ2 channel are predicted to form multiple hydrogen bonds and hydrophobic interactions with Picrotoxinin, whereas the proline residues in the 2' positions of ρ1 channels are predicted to form only hydrophobic contacts with Picrotoxinin. However, although the studied ρ1 P2'G, A, and V models form no hydrogen bonds with Picrotoxinin, they may participate in several hydrophobic interactions, and the ligand may have distinctive binding modes with GABAA-ρ mutant channels. Picrotoxinin has a lower Emodel value with ρ2 than ρ1 homomeric models (-47Kcal/mol and -36Kcal/mol, respectively), suggesting that picrotoxin blocks the pores of the ρ2 channels more effectively.
Picrotoxinin receptor ligand blocks anti-punishment effects of alcohol
Alcohol 1988 Nov-Dec;5(6):437-43.PMID:2854473DOI:10.1016/0741-8329(88)90079-1.
Ethanol at low doses produces a release of punished responding in an operant rat conflict test similar to that observed for benzodiazepines and phenobarbital. It has been hypothesized that these anti-punishment effects are mediated via the GABA-benzodiazepine receptor-ionophore complex but not at the benzodiazepine binding site. In the present study isopropylbicyclophosphate (IPPO), which binds at the Picrotoxinin site, reversed the release of punished responding produced by ethanol, pentobarbital and chlordiazepoxide; at low doses IPPO (less than 10 micrograms/kg) appeared to be most effective against ethanol but at higher doses (greater than 15 micrograms/kg) was also effective against pentobarbital and chlordiazepoxide. At still higher doses IPPO produced a decrease in punished and unpunished responding. These results suggest that the "anxiolytic" actions of ethanol may involve a direct action on the GABA-benzodiazepine receptor-ionophore complex and this action may underlie some of the intoxicating effects of ethanol.
Comparison of the toxicokinetics of the convulsants Picrotoxinin and tetramethylenedisulfotetramine (TETS) in mice
Arch Toxicol 2020 Jun;94(6):1995-2007.PMID:32239239DOI:10.1007/s00204-020-02728-z.
Acute intoxication with picrotoxin or the rodenticide tetramethylenedisulfotetramine (TETS) can cause seizures that rapidly progress to status epilepticus and death. Both compounds inhibit γ-aminobutyric acid type-A (GABAA) receptors with similar potency. However, TETS is approximately 100 × more lethal than picrotoxin. Here, we directly compared the toxicokinetics of the two compounds following intraperitoneal administration in mice. Using LC/MS analysis we found that Picrotoxinin, the active component of picrotoxin, hydrolyses quickly into picrotoxic acid, has a short in vivo half-life, and is moderately brain penetrant (brain/plasma ratio 0.3). TETS, in contrast, is not metabolized by liver microsomes and persists in the body following intoxication. Using both GC/MS and a TETS-selective immunoassay we found that mice administered TETS at the LD50 of 0.2 mg/kg in the presence of rescue medications exhibited serum levels that remained constant around 1.6 μM for 48 h before falling slowly over the next 10 days. TETS showed a similar persistence in tissues. Whole-cell patch-clamp demonstrated that brain and serum extracts prepared from mice at 2 and 14 days after TETS administration significantly blocked heterologously expressed α2β3γ2 GABAA-receptors confirming that TETS remains pharmacodynamically active in vivo. This observed persistence may contribute to the long-lasting and recurrent seizures observed following human exposures. We suggest that countermeasures to neutralize TETS or accelerate its elimination should be explored for this highly dangerous threat agent.
Blocking actions of Picrotoxinin analogues on insect (Periplaneta americana) GABA receptors
Neurosci Lett 1994 Apr 25;171(1-2):67-9.PMID:7916140DOI:10.1016/0304-3940(94)90606-8.
Five Picrotoxinin analogues were examined on GABA-gated chloride channels of an identifiable cockroach (Periplaneta americana) motor neurone (Df). Substitution of the bridgehead hydroxyl at the C-6 position of the Picrotoxinin molecule by a fluorine atom (fluoropicrotoxinin) had little effect, whereas acetylation of the same functional group (Picrotoxinin acetate) substantially reduced the effectiveness of the parent compound. Conversion of the terminal isopropenyl group to an acetyl (alpha-picrotoxinone) or hydration of the double bond (picrotin) also reduced activity. Dendrobine, a naturally-occurring picrotoxinin-like compound had very little effect on GABA-induced responses at concentrations up to 1.0 x 10(-5) M. The present results suggest that the size and the ability of the bridgehead hydroxyl to undergo hydrogen bond formation and the lipophilic nature of the terminal isopropenyl group profoundly affect the inhibitory actions of the Picrotoxinin molecule on insect neuronal GABA-gated chloride channels.