Muscimol

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Muscimol
Muscimol chemical structure.svg
Muscimol3d.png
Identifiers
CAS number 2763-96-4 N
PubChem 4266
ChemSpider 4116 YesY
ChEMBL CHEMBL273481 YesY
Jmol-3D images Image 1
Properties[1]
Molecular formula C4H6N2O2
Molar mass 114.10 g mol−1
Melting point 184 to 185 °C (363 to 365 °F; 457 to 458 K)
Solubility in water very soluble
Solubility in ethanol slightly soluble
Solubility in methanol very soluble
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

Muscimol (also known as agarin or pantherine) is the principal psychoactive constituent of Amanita muscaria and related species of mushroom. Muscimol acts as a potent, selective agonist for the GABAA receptors and displays sedative-hypnotic and dissociative psychoactivity.

Chemistry[edit]

Muscimol is the psychoactive compound responsible for the effects of Amanita muscaria intoxication. Ibotenic acid, a neurotoxic secondary metabolite of Amanita muscaria, serves as a prodrug to muscimol when the mushroom is ingested or dried, converting to muscimol via decarboxylation.

Biology[edit]

Muscimol is produced naturally in the mushrooms Amanita muscaria and Amanita pantherina, along with muscarine, muscazone, and ibotenic acid.[2][3] A. muscaria and A. pantherina should be eaten with caution and prepared properly to lessen effects of nausea; no official deaths from poisoning have been recorded from A. muscaria and A. pantherina.[4] In A. muscaria, the layer just below the skin of the cap contains the highest amount of muscimol, and is therefore the most psychoactive portion.[5]

Amanita muscaria, which contains muscimol

Pharmacology[edit]

Muscimol is a potent GABAA agonist, activating the receptor for the brain's principal inhibitory neurotransmitter, GABA. Muscimol binds to the same site on the GABAA receptor complex as GABA itself, as opposed to other GABAergic drugs such as barbiturates and benzodiazepines which bind to separate regulatory sites.[6] GABAA receptors are widely distributed in the brain, and so when muscimol is administered, it alters neuronal activity in multiple regions including the cerebral cortex, hippocampus, and cerebellum.

While muscimol is conventionally thought of as a selective GABAA agonist, it is also a partial agonist at the GABAA-rho receptor, and so its range of effects results from a combined action at both targets.[7]

In patients with Huntington's disease and chronic schizophrenia, oral doses of muscimol have been found to cause a rise of both prolactin and growth hormone.[8]

During a test involving rabbits connected to an EEG, muscimol presented with a distinctly synchronized EEG tracing. This is substantially different from serotonergic psychedelics, with which brainwave patterns generally show a desynchronization. In higher doses (2 mg/kg), the EEG will show characteristic spikes.[citation needed]

When consumed, some percentage of muscimol goes un-metabolized and thus excreted in urine, a phenomenon exploited by practitioners of the traditional entheogenic use of Amanita muscaria.[9]

The psychoactive dose of muscimol is around 10–15 mg for a normal person.[10] A Guide to British Psilocybin Mushrooms by Richard Cooper published in 1977 recommends a smaller dose, 8.5 mg, and suggests that it is possible for this amount to be present in as little as 1 g of dried A. muscaria. A correct dose may be difficult to determine because potency varies dramatically from one mushroom to the next.

Toxicity[edit]

The LD50 in mice is 3.8 mg/kg s.c, 2.5 mg/kg i.p.[11] The LD50 in rats is 4.5 mg/kg i.v, 45 mg/kg orally.[11]

Effects[edit]

Many of muscimol's effects are consistent with its pharmacology as a GABAA receptor agonist, presenting many depressant or sedative-hypnotic effects. Atypical of the effect profile of sedative drugs generally however, muscimol, like Z-drugs, can cause dissociative changes in perception.[citation needed][12] Jonathan Ott describes the effects of Amanita pantherina below:

See also[edit]

Notes[edit]

  1. ^ The Merck Index, 12th Edition
  2. ^ Chilton, WS; Ott, J (1976). "Toxic metabolites of Amanita pantherina, A. Cothurnata, A. Muscaria and other Amanita species". Lloydia 39 (2–3): 150–7. PMID 985999. 
  3. ^ Michelot, D; Melendez-Howell, LM (2003). "Amanita muscaria: chemistry, biology, toxicology, and ethnomycology". Mycological Research 107 (Pt 2): 131–46. doi:10.1017/S0953756203007305. PMID 12747324. 
  4. ^ Tupalska-Wilczyńska, K; Ignatowicz, R; Poziemski, A; Wójcik, H; Wilczyński, G (1996). "Poisoning with spotted and red mushrooms--pathogenesis, symptoms, treatment". Wiadomości Lekarskie (in Polish) 49 (1–6): 66–71. PMID 9173659. 
  5. ^ Chilton, WS (1978). "Chemistry and Mode of Action of Mushroom Toxins". In Rumack, BH; Salzman, E. Mushroom Poisoning: Diagnosis and Treatment. Palm Beach: CRC Press. pp. 87–124. ISBN 9780849351853. 
  6. ^ Frølund, B; Ebert, B; Kristiansen, U; Liljefors, T; Krogsgaard-Larsen, P (2002). "GABA-A receptor ligands and their therapeutic potentials". Current Topics in Medicinal Chemistry 2 (8): 817–32. doi:10.2174/1568026023393525. PMID 12171573. 
  7. ^ Woodward, RM; Polenzani, L; Miledi, R (1993). "Characterization of bicuculline/baclofen-insensitive (rho-like) gamma-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of gamma-aminobutyric acidA and gamma-aminobutyric acidB receptor agonists and antagonists". Molecular Pharmacology 43 (4): 609–25. PMID 8386310. 
  8. ^ Tamminga, CA; Neophytides, A; Chase, TN; Frohman, LA (1978). "Stimulation of prolactin and growth hormone secretion by muscimol, a gamma-aminobutyric acid agonist". The Journal of Clinical Endocrinology and Metabolism 47 (6): 1348–51. doi:10.1210/jcem-47-6-1348. PMID 162520. 
  9. ^ Goldstein A. (2001). Addiction: From Biology to Drug Policy. Oxford University Press. p. 228. ISBN 978-0-19-514664-6. 
  10. ^ Erowid Psychoactive Amanitas Vault : Dosage
  11. ^ a b Erowid Psychoactive Amanitas Vault : Chemistry
  12. ^ http://www.erowid.org/plants/amanitas/amanitas_effects.shtml
  13. ^ Jonathan Ott (Jun 11, 2000). "Studies of Amanita: experience with Amanita muscaria (ID 366)". Erowid.org. 

References[edit]

  • Ito Y, Segawa K, Fukuda H (1995). "Functional diversity of GABAA receptor ligand-gated chloride channels in rat synaptoneurosomes". Synapse 19 (3): 188–96. doi:10.1002/syn.890190306. PMID 7784959. 
  • Rätsch, Christian. (1998). The Encyclopedia of Psychoactive Plants. Rochester, VT: Park Street Press.
  • Beaumont K, Chilton W. S., Yamamura H. I., Enna S. J. (1978). "Muscimol binding in rat brain: association with synaptic GABA receptors". Brain Res. 148 (1): 153–62. doi:10.1016/0006-8993(78)90385-2. PMID 207386. 
  • S. R. Snodgrass (1978). "Use of 3H-muscimol for GABA receptor studies". Nature 273 (1): 392–394. doi:10.1038/273392a0. 
  • G. A. R. Johnston, D. R. Curtis, W. C. de Groat and A. W. Duggan (1968). "Central actions of ibotenic acid and muscimol". Biochemical Pharmacology 17 (12): 2488–2489. doi:10.1016/0006-2952(68)90141-X. PMID 5752907. 
  • Tamminga CA, Neophytides A, Chase TN, Frohman LA (December 1978). "Stimulation of prolactin and growth hormone secretion by muscimol, a gamma-aminobutyric acid agonist". J. Clin. Endocrinol. Metab. 47 (6): 1348–51. doi:10.1210/jcem-47-6-1348. PMID 162520. 

External links[edit]