Picrotoxin

Overview

Picrotoxin, also known as cocculin, is a poisonous crystalline plant compound. It was first isolated by the French pharmacist and chemist Pierre François Guillaume Boullay (1777–1869) in 1812. The name "picrotoxin" is a combination of the Greek words "picros" (bitter) and "toxicon" (poison). A mixture of two different compounds, picrotoxin occurs naturally in the fruit of the Anamirta cocculus plant, although it can also be synthesized chemically.[1][2] WP

Due to its interactions with the inhibitory neurotransmitter GABA, picrotoxin acts as a stimulant and convulsant. It mainly impacts the central nervous system, causing seizures and respiratory paralysis in high enough doses. WP

Risks and side effects

Toxicity

Picrotoxin acts as a central nervous system and respiratory stimulant. It is extremely toxic to fish and humans, as well as rodents and other mammals. According to the Register of Toxic Effects of Chemical Substances, the LDLo, or lowest reported lethal dose, is 0.357 mg/kg. Symptoms of picrotoxin poisoning include coughing, difficulty breathing, headache, dizziness, confusion, gastro-intestinal distress, nausea or vomiting, and changes in heart rate and blood pressure. Although especially dangerous if swallowed, systemic effects can also result from inhalation or absorption into the blood stream through lesions in the skin. Picrotoxin also acts as a convulsant. In larger doses, it has been found to induce clonic seizures or cardiac dysrhythmias, with especially high doses ultimately proving fatal, typically due to respiratory paralysis.[3][4] WP

Pharmacology

Mechanism of action

Some crustacean muscle fibers have excitatory and inhibitory innervation. Picrotoxin blocks inhibition. Two different but related theories have been proposed for the mechanism by which picrotoxin acts on synapses. One theory is that it acts as a non-competitive channel blocker for GABAA receptor chloride channels, specifically the gamma-aminobutyric acid-activated chloride ionophore. A 2006 study found that, while not structurally similar to GABA, picrotoxin prevents ion flow through the chloride channels activated by GABA. It likely acts within the ion channels themselves, rather than at GABA recognition sites. Because it inhibits channels activated by GABA, GABA-enhancing drugs like barbiturates and benzodiazepines can be used as an antidote.[5–8] WP

Other research suggests that the toxin acts instead as a non-competitive antagonist, or inhibitor, for GABA receptors. A study by Newland and Cull-Candy found that, in high enough concentrations, picrotoxin reduced the amplitude of GABA currents. Their data indicated that it was unlikely that picrotoxin acted simply as a voltage-gated channel blocker, although it did reduce the frequency of channel openings. Rather, they found that picrotoxin “binds preferentially to an agonist bound form of the receptor.” This means that, even in the presence of low concentrations of picrotoxin, the response of neurons to GABA is reduced.[9] WP

Chemistry

Formula

C30H34O13 PC

Molar mass (g/mol)

602.6 PC

IUPAC name (computed by PubChem)

(1R,3S,5S,8S,13R,14S)-1-hydroxy-14-(2-hydroxypropan-2-yl)-13-methyl-4,7,10-trioxapentacyclo[6.4.1.19,12.03,5.05,13]tetradecane-6,11-dione;(1R,5S,8S,13R,14R)-1-hydroxy-13-methyl-14-prop-1-en-2-yl-4,7,10-trioxapentacyclo[6.4.1.19,12.03,5.05,13]tetradecane-6,11-dione PC

SMILES

CC(=C)[C@@H]1C2[C@@H]3[C@@]4([C@](C1C(=O)O2)(CC5[C@]4(O5)C(=O)O3)O)C.C[C@@]12[C@H]3C4[C@H](C([C@@]1(C[C@H]5[C@]2(O5)C(=O)O3)O)C(=O)O4)C(C)(C)O PC

InChIKey

VJKUPQSHOVKBCO-HOYQAQCQSA-N PC

PubChem CID

5360688

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Boullay PF. Analyse chimique de la Coque du Levant, Menispermum cocculus. Bulletin de Pharmacie. 1812
2. Other (Boullay, 1812), p. 31
3. Other Picrotoxin
4. Journal / agency Picrotoxin
5. Journal / agency Van Der Kloot WG, Robbins J, Cooke IM. Blocking by picrotoxin of peripheral inhibition in crayfish. Science. March 1958. doi:10.1126/science.127.3297.521 · PMID 13529017
6. Journal / agency Rho JM, Donevan SD, Rogawski MA. Direct activation of GABAA receptors by barbiturates in cultured rat hippocampal neurons. The Journal of Physiology. December 1996. doi:10.1113/jphysiol.1996.sp021784 · PMID 8961191 · PMC1161000
7. Harm reduction site Law V, Knox C, Djoumbou Y, Jewison T, Guo AC, Liu Y, Maciejewski A, Arndt D, Wilson M, Neveu V, Tang A. Picrotoxin
8. Journal / agency Olsen RW. Picrotoxin-like channel blockers of GABAA receptors. Proceedings of the National Academy of Sciences of the United States of America. April 2006. doi:10.1073/pnas.0601121103 · PMID 16606858 · PMC1458832
9. Journal / agency Newland CF, Cull-Candy SG. On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat. The Journal of Physiology. February 1992. doi:10.1113/jphysiol.1992.sp018998 · PMID 1317428 · PMC1176032

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.