Picrotoxin (124-87-8) Physical and Chemical Properties
Picrotoxin
Plant-derived sesquiterpene dilactone mixture used primarily as a research reagent and reference standard for neuropharmacology and GABA-A receptor studies.
| CAS Number | 124-87-8 |
| Family | Sesquiterpene dilactones |
| Typical Form | Microcrystalline powder or prismatic crystals |
| Common Grades | BP, EP, USP |
Picrotoxin is a naturally derived sesquiterpene-derived molecular complex comprising two dilactone components (picrotoxinin and picrotin) in an approximately 1:1 association. Structurally it is best described as a non‑nitrogenous neutral molecular compound formed from two highly oxygenated bicyclic/dilactone frameworks; the combined molecular formula is reported as C15H18O7·C15H16O6 (often written as C30H34O13 for the 1:1 complex). The compound presents multiple stereocenters and several fused ether and lactone rings that create a compact, rigid polycyclic architecture with limited conformational flexibility (covalently‑bonded unit count = 2; rotatable bond count = 2).
Electronically, picrotoxin is highly polar for a terpenoid: it carries multiple carbonyl and ether oxygen atoms giving a large hydrogen‑bond acceptor capacity and a modest number of hydrogen‑bond donors. The computed topological polar surface area (TPSA) is 191 \(\text{Å}^2\) and the hydrogen‑bond acceptor count is 13 with 3 donors, consistent with low membrane partitioning and relatively high aqueous affinity for a terpene natural product. The reported octanol–water partition coefficient (logP) is \(-2.229\), indicating net hydrophilicity under neutral conditions. Picrotoxin is a neutral, nonbasic, nonacidic molecule in standard aqueous media (a saturated aqueous solution is reported as neutral to litmus) and is not an ionizable small molecule in the physiological pH range.
Functionally, picrotoxin is a potent central nervous system (CNS) active convulsant that acts as a noncompetitive antagonist of GABA\(_A\) receptor‑gated chloride channels. Historically it has been used as a research tool, and it has seen limited and largely discontinued medicinal use as a respiratory stimulant and antidote for barbiturate poisoning because of its narrow therapeutic index. Common commercial grades reported for this substance include: BP, EP, USP.
Basic Physicochemical Properties
Density and Solid-State Form
Pure material is described as colorless, shining, prismatic crystals or white to nearly white microcrystalline powder and occasionally as shiny rhomboid leaflets. The solid state consists of the 1:1 molecular complex of picrotoxinin and picrotin; the record reports a covalently‑bonded unit count of 2 consistent with a molecular complex rather than a single small‑molecule monomer. No absolute solid‑state density value is provided in the current data context.
Melting Point
Reported experimental melting points are provided as: 397 \(^\circ\)F (EPA, 1998); 203.5; and 203 \(^\circ\)C. No single consensus melting point uncertainty is supplied beyond these entries.
Solubility and Dissolution Behavior
Reported experimental solubility observations include: - "1 g in 350 ml water" - "1 g in 5 ml boiling water (approx)" - "1 g in 13.5 ml 95% ethanol" - "1 g in 3 ml boiling alcohol (approx)" An additional numeric solubility entry "4100" is present in the raw data without explicit units. Practical interpretation of the listed values indicates moderate solubility in cold water, substantially increased solubility in hot water and in hot alcohol, and appreciable solubility in high‑strength ethanol. A saturated aqueous solution is reported as neutral to litmus, consistent with a nonionizable neutral compound.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
Picrotoxin is a nonnitrogenous neutral compound; a saturated aqueous solution is neutral to litmus. No experimentally established \(\mathrm{p}K_a\) value for picrotoxin is available in the current data context.
Reactivity and Stability
Picrotoxin is described as stable in air but is affected by light; protection from light is recommended for storage. It may react with strong oxidizing or reducing agents. Thermal decomposition produces acrid smoke and fumes. Chemically, picrotoxin can be regarded as a pair of dilactone structures (picrotoxinin and picrotin); the two components have different activity (picrotoxinin is the principal active convulsant while picrotin is largely inactive). The presence of multiple lactone and ether functionalities implies susceptibility to hydrolytic cleavage under strong acid or base conditions and potential sensitivity to nucleophilic or reductive degradations at labile carbonyl centers; however, no quantitative hydrolysis rates or kinetic data are provided in the current data context.
Molecular Parameters
Molecular Weight and Formula
- Combined molecular formula (reported): C15H18O7·C15H16O6
- Also reported as: C30H34O13
- Computed molecular weight: 602.6 (reported value)
The combined exact/monoisotopic mass is given as 602.19994113.
LogP and Structural Features
- Reported logP: \(-2.229\)
The negative logP corresponds to low octanol partitioning and supports the high polar surface area and high hydrogen‑bonding capacity (HB acceptors = 13; HB donors = 3; TPSA = 191 \(\text{Å}^2\)). Structurally, the molecule contains multiple fused lactone rings and ether bridges that generate a rigid, three‑dimensional scaffold with limited rotatable bonds (rotatable bond count = 2) and many defined stereocenters (defined atom stereocenter count = 11). These features reduce conformational flexibility and influence binding interactions at the GABA receptor chloride channel.
Structural Identifiers (SMILES, InChI)
- SMILES: CC(=C)[C@@H]1C2[C@@H]3[C@@]4(C@(CC5[C@]4(O5)C(=O)O3)O)C.C[C@@]12[C@H]3C4C@HC(C)(C)O
- InChI: InChI=1S/C15H18O7.C15H16O6/c1-12(2,18)6-7-10(16)20-8(6)9-13(3)14(7,19)4-5-15(13,22-5)11(17)21-9;1-5(2)7-8-11(16)19-9(7)10-13(3)14(8,18)4-6-15(13,21-6)12(17)20-10/h5-9,18-19H,4H2,1-3H3;6-10,18H,1,4H2,2-3H3/t5-,6+,7?,8?,9-,13-,14-,15+;6?,7-,8?,9?,10+,13+,14+,15-/m10/s1
- InChIKey: VJKUPQSHOVKBCO-ZTYBEOBUSA-N
All structural identifiers above are presented as supplied and reflect the two‑component covalent assembly typical for picrotoxin samples.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS Number: 124-87-8
- European Community (EC) Number: 204-716-6
- UN Number (listed in some transport summaries): 3462 (COCCULUS)
- DrugBank ID (reported): DB00466
- InChIKey: VJKUPQSHOVKBCO-ZTYBEOBUSA-N
These identifiers are reported for cross‑reference and sample tracking.
Synonyms and Brand-Independent Names
Reported synonyms and common names include: - Picrotoxin - Cocculin - Cocculus - Picrotoxinin–picrotin (1:1) - Picrotoxinin - Picrotin - Picrotoxine - Picrotox
(The list above reflects commonly used names appearing in supplier and regulatory annotations.)
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Picrotoxin is primarily a bioactive convulsant that functions as a noncompetitive antagonist at GABA\(_A\) receptor chloride channels. Its principal roles in practice are as a pharmacological tool for neuroscience research (to probe inhibitory chloride conductance and GABAergic signaling) and historically as a medicinal agent employed as a CNS stimulant and as an antidote in barbiturate poisoning. Clinical use has declined due to its high toxicity and narrow therapeutic window; it is not considered a broadly useful therapeutic agent.
Formulation and Development Contexts
In formulation contexts, picrotoxin has been handled as a pure crystalline material or as extracted natural product mixtures (seeds/berry extracts). Given its potency and toxicity, formulations for research or veterinary use emphasize precise dosing and containment; specific excipient compatibility, delivery forms, and validated formulation parameters are not provided in the current data context. No concise industrial manufacturing specifications are supplied here beyond statements that the compound is derived by extraction from seeds of Anamirta paniculata (Cocculus indicus/fishberries) or related natural sources.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Common commercial grades reported for picrotoxin include: BP, EP, USP. These grade labels indicate that analytical and pharmacopoeial quality specifications are referenced in some supply chains. Typical grade categories encountered in practice for this class of substances are pharmaceutical (pharmacopoeial), analytical/reagent, and technical/research‑grade material.
General Quality Attributes (Qualitative Description)
Key quality attributes relevant to procurement and QC include: - Identity and purity (confirmation of the picrotoxinin:picrotin ratio and absence of other seed‑derived alkaloids). - Physical form (crystalline leaflets or microcrystalline powder) and associated bulk density/particle size for handling. - Stability to light and heat (product is light sensitive and decomposes on strong heating). - Residual solvent content when provided from extraction processes. Specific assay limits, impurity thresholds, or certificate of analysis values are not provided in the current data context and should be obtained from supplier documentation for any procurement or regulatory use.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
Picrotoxin is highly toxic. Reported acute effects include CNS stimulation with potential for severe convulsions; a dose of \(20\,\mathrm{mg}\) may produce symptoms of severe poisoning, and a human lethal dose has been reported as approximately \(1.5\,\mathrm{mg}\,\mathrm{kg}^{-1}\) in one context. Clinical signs of acute exposure may include headache, salivation, sweating, pupillary dilation, visual disturbance, muscle rigidity, hyperactivity, delirium, hallucinations, nausea, vomiting, respiratory distress, pulmonary edema, convulsions and coma. Because of its convulsant action, picrotoxin use is contraindicated when alternative supportive measures are available; it should not be administered where stimulant therapy may be hazardous. The material is also highly toxic to aquatic life (notably fish).
Occupational controls and personal protective measures should assume high acute toxicity: avoid ingestion, inhalation and skin contact; use appropriate engineering controls (local exhaust, containment) and wear suitable PPE including gloves, eye/face protection, and, for emergency response, respiratory protection (supplied‑air or positive‑pressure breathing apparatus) and fully encapsulating suits as required by the exposure scenario.
Storage and Handling Guidelines
- Store protected from light and in tightly closed containers to minimize degradation.
- Control access and maintain rigorous procedures for weighing, transfer, and waste handling to avoid accidental exposure or environmental release.
- Spills should be isolated, personnel evacuated as appropriate, and decontamination performed using absorbent materials and appropriate PPE; contaminated materials should be collected for disposal following applicable hazardous waste regulations.
- On heating or decomposition, the material emits acrid fumes; avoid exposure to decomposition products. For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
