Picrotoxin

602.58

602.199941

204-716-6

3462|2811

DTXSID7045605

Shiny rhomboid leaflets|Colorless, shining, prismatic crystals or white or nearly white microcrystalline powder

29322985

190.95000

-2.229

white to light yellow powder

1,28 g/cm 3

203 °C

571.75°C (rough estimate)

1.6000 (estimate)

ethanol: 50 mg/mL, clear to slightly hazy

Store at RT

Intraperitoneal-rat LD50: 1.99 mg/kg; oral-mouse LD50: 15 mg/kg

Non-flammable

D16 -29.3° (c = 4 in abs ethanol)

Odorless

Very bitter

A saturated solution in water is neutral to litmus

Picrotoxin is a nonnitrogenous neutral cmpd that can be broken down into two dilactones, picrotoxinin and picrotin; the latter is inactive

No rapid reaction with air No rapid reaction with water

Alcohols and Polyols

COCCULUS contains picrotoxin, a molecular compound of picrotoxinin and picrotin. May react with strong oxidizing agents and with strong reducing agents.

I

6.1(a)

UN 3462 6.1/PG 2

3

28-52/53

28-36/37/39-45-61

TJ9100000

T+,T,N

Treasury is ventilated, low temperature and dry; store and transport separately from food

Very Toxic

Stable in air; affected by light

P264-P301 + P310

H300

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

When heated to decomposition it emits acrid smoke and fumes. Avoid decomposing heat. (EPA, 1998)

|Danger|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 43 companies from 1 notifications to the ECHA C&L Inventory.

(Non-Specific -- Alkaloid) Isolate hazard area and deny entry. Wear positive pressure breathing apparatus and special protective clothing. (Non-Specific -- Alkaloid) Use dry chemical, carbon dioxide, water spray, or foam for small fires. Use water spray, fog, or foam for large fires. Move container from fire area if this can be done without risk. (EPA, 1998)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

(Non-Specific -- Alkaloid) Keep unnecessary people away; isolate hazard area and deny entry. Stay upwind; keep out of low areas. Ventilate closed spaces before entering them. Remove and isolate contaminated clothing at the site. If water pollution occurs, notify appropriate authorities. Do not touch spilled material; stop leak if you can do it without risk. Use water spray to reduce vapors. Small spills: take up with sand or other noncombustible absorbent material and place into containers for later disposal. Small dry spills: with clean shovel place material into clean, dry container and cover; move containers from spill area. Large spills: dike far ahead of spill for later disposal. (EPA, 1998)

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Picrotoxin is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500/10,000 lbs.

most toxic

Oral, mouse: LD50 = 15 mg/kg. In large doses it is a powerful poison, causing unconsciousness, delirium, convulsions, gastro-enteritis and stimulation of the respiratory centre followed by paralysis, from which death sometimes results.

Picrotoxin is obtained from Anamirta cocculus, a climbing shrub indigenous to Malabar and the East Indies. The drug is present in the seeds of the plant, commonly known as fishberries ...|/Picrotoxin can be/ ... isolated from the seed of ... Tinomiscium philippinense ...

Used internally for relieving respiratory distress. Also for use as an antidote in poisoning by CNS depressants, especially barbiturates.

Antidotes; Central Nervous System Stimulants; Convulsants; GABA Antagonists|Formerly employed in the treatment of poisoning by central nervous system depressants, picrotoxin is not a selective respiratory stimulant and is not regarded as a useful therapeutic agent.|MEDICATION (VET): Central nervous system stimulant, antidote to barbiturates

Picrotoxin is a highly toxic substance, and a dose of 20 mg may produce symptoms of severe poisoning.|Picrotoxin and similar agents may cause convulsions and should not be used to treat phenothiazine overdoses and should not be admin at other times when a stimulant is needed.|With large doses of picrotoxin a tonic-clonic seizure may occur in which tonic flexion precedes tonic extension. Accompanying the convulsive movements are salivation, elevation of blood pressure due to vasomotor stimulation, and frequently emesis.|Picrotoxin is a powerful stimulant and affects all portions of the central nervous system.

Picrotoxin is a toxin obtained from the seeds of the shrub Anamirta cocculus. It is used as a central nervous system stimulant, antidote, convulsant, and GABA (gamma aminobutyric acid) antagonist. It is a noncompetitive antagonist at GABA_A receptors and thus a convulsant. Picrotoxin blocks the GABA_Activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially barbiturates.

Agents counteracting or neutralizing the action of POISONS. (See all compounds classified as Antidotes.)|A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. (See all compounds classified as Central Nervous System Stimulants.)|Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS. (See all compounds classified as GABA Antagonists.)|Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. (See all compounds classified as Convulsants.)

Although picrotoxin is absorbed by all routes, the full effect on the central nervous system is not seen for several minutes, even when the drug is admin intravenously. Its duration action is relatively brief.

Picrotoxin antagonizes the GABA_A receptor channel directly, which is a ligand-gated ion channel concerned chiefly with the passing of chloride ions across the cell membrane. Therefore picrotoxin prevents Cl^- channel permeability and thus promtes an inhibitory influence on the target neuron. Picrotoxin reduces conductance through the channel by reducing not only the opening frequency but also the mean open time. Picrotoxin also antagonizes GABA_C receptors (also called GABA_A-rho receptors) but the result of this action is not known. The GABA_C receptor is also linked to chloride channels, with distinct physiological and pharmacological properties. In contrast to the fast and transient responses elicited from GABA_A receptors, GABA_C receptors mediate slow and sustained responses.|In mammals it has been shown that picrotoxin blocks presynaptic inhibition and strychnine-resistant postsynaptic inhibition in the central nervous system. Picrotoxin selectively antagonizes the effects of the predominant inhibitory transmitter, gamma-aminobutyric (GABA), at all levels of the central nervous system. Current information indicates that GABA receptors are coupled to ionophores that permit the influx of chloride with resultant hyperpolarization of neuronal membranes. Picrotoxin antagonizes the effects of GABA, perhaps by interacting with sites closely associated with the ionophore. A similarly acting convulsant drug, bicuculline, interacts directly with the GABA receptor and is therefore a true antagonist. Both drugs produce convulsions by blocking the inhibitory pathways mediated by GABA. The relative importance of blockade of presynaptic or postsynaptic inhibition for their convulsant activity is unknown.

Highly toxic and a dose of 20 mg may produce symptoms of severe poisoning. A human lethal dose of 1.5 mg/kg has been reported. It is an alkaloid convulsant poison. (EPA, 1998)

Warning: Picrotoxin is a powerful stimulant and affects all portions of the central nervous system. Picrotoxin is a highly toxic alkaloid convulsant poison. Epileptics may be more sensitive to picrotoxin. Signs and Symptoms of Picrotoxin Exposure: Signs and symptoms of acute exposure to picrotoxin may include slowing of pulse followed by increased pulse rate, tachycardia, and arrhythmias. Headache, salivation, sweating, dilation of pupils, loss of vision, muscle rigidity, excitement, hyperactivity, delirium, hallucinations, and convulsions may be observed. Nausea, vomiting, diarrhea, hyperpnea (excessive respiration), pulmonary edema, respiratory failure, and coma may also be noted. Emergency Life-Support Procedures: Acute exposure to picrotoxin may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination. Inhalation Exposure: 1. Move victims to fresh air. Emergency personnel should avoid self-exposure to picrotoxin. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support. 3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 4. Rush to a health care facility. Dermal/Eye Exposure: 1. Remove victims from exposure. Emergency personnel should avoid self-exposure to picrotoxin. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support. 3. Remove and isolate contaminated clothing as soon as possible. 4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes. 5. Wash exposed skin areas three times with soap and water. Speed in removing picrotoxin from the skin is of extreme importance. 6. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 7. Rush to a health care facility. Ingestion Exposure: 1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support. 2. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 3. Vomiting may be induced with syrup of Ipecac. If elapsed time since ingestion of picrotoxin is unknown or suspected to be greater than 30 minutes, do not induce vomiting and proceed to Step 4. Ipecac should not be administered to children under 6 months of age.Warning: Ingestion of picrotoxin may result in sudden onset of seizures or loss of consciousness. Syrup of Ipecac should be administered only if victims are alert, have an active gag-reflex, and show no signs of impending seizure or coma. If ANY uncertainty exists, proceed to Step 4.The following dosages of Ipecac are recommended: children up to 1 year old, 10 mL (1/3 oz); children 1 to 12 years old, 15 in mL (1/2 oz); adults, 30 mL (1 oz). Ambulate (walk) the victims and give large quantities of water. If vomiting has not occurred after 15 minutes, Ipecac may be readministered. Continue to ambulate and give water to the victims. If vomiting has not occurred within 15 minutes after second administration of Ipecac, administer activated charcoal. 4. Active charcoal may be administered if victims are conscious and alert. Use 15 to 30 g (1/2 to 1 oz) for children, 50 to 100 g (1-3/4 to 3-1/2 oz) for adults, with 125 to 250 mL (1/2 to 1 cup) of water. 5. Promote excretion by administering a saline cathartic or sorbitol to conscious and alert victims. Children require 15 to 30 g (1/2 to 1 oz) of cathartic; 50 to 100 g (1-3/4 to 3-1/2 oz) is recommended for adults. 6. Rush to health care facility. (EPA, 1998)

An unusual case of poisoning with eye involvement occurred in a young woman who ate fish that had been killed by picrotoxin. She developed headache, chills, salivation, and loss of vision, with the pupils dilated and unreactive. Both retinas were observed to be edematous. ... The patient recovered ...|No appreciable effect of picrotoxin is seen until convulsive doses are given. The resultant convulsion is clonic and incoordinated, and the pattern resembles that produced by pentylenetetrazol ... With large doses of picrotoxin a tonic-clonic seizure may occur in which tonic flexion precedes tonic extension. Accompanying the convulsive movements are salivation, elevation of blood pressure due to vasomotor stimulation, and frequently emesis.|Picrotoxin is a highly toxic substance, and a dose of 20 mg may produce symptoms of severe poisoning. The fatal dose for man is unknown.

Picrotoxin