https://en.wikipedia.org/wiki/Muscimol hentet 30. nov. 2017:
muscimol 
Muscimol kemisk struktur .svg
Muscimol kemisk struktur .
Muscimol3d.png
Muscimol 3d model
IUPAC-navn
5- (aminomethyl) -isoxazol-3-ol
Kemisk formel
C 4 H 6 N 2 O 2
Opløselighed i vand
meget opløselig
Opløselighed i ethanol
let opløselig
Opløselighed i methanol
meget opløselig
- AU: S9 (Forbudt)
Muscimol (også kendt som agarin eller pantherin ) er den vigtigste psykoaktive bestanddel af Amanita muscaria og beslægtede svampearter . Muscimol er en potent, selektiv agonist for GABA(A)-receptorerne og viser sedativ-hypnotisk ,depressiv og dissociativ psykoaktivitet .
Muscimol er den psykoaktive forbindelse, der er ansvarlig for virkningerne af Amanita muscaria- forgiftning.
Iboteninsyre er en neurotoksisk sekundær metabolit af Amanita muscaria , og tjener som et prodrug til dannelse af muscimol, når svampen indtages (omsættes i kroppen) eller tørres. Omdannelse til muscimol sker via decarboxylering .
Muscimol dannes i svampen Amanita muscaria (Rød fluesvamp) og Amanita pantherina , sammen med muscarin ,muscazone og ibotensyre . [2 ] [3 ]
A. muscaria og A. pantherina bør spises med forsigtighed og tilberedes ordentligt for at mindske virkningerne af kvalme;
ingen officielle dødsfald fra forgiftning er blevet noteret fra A. muscaria og A. pantherina . [4 ]
A. muscaria indeholder laget lige under skindet på hatten den højeste mængde muscimol og denne del af svampen er derfor den mest psykoaktive del. [5 ]
Farmakologi
Muscimol er en potent GABA(A)-agonist , der aktiverer receptorer forGABA , der er hjernens primære inhibitoriske neurotransmitter .
Muscimol binder til det samme sted på GABA(A)-receptorkomplekset som GABA selv, i modsætning til andre GABAergiske lægemidler, såsom barbiturater og benzodiazepiner, der binder til separate reguleringssteder. [6]
GABA-receptorer er bredt fordelt i hjernen, og når hjernen påvirkes af muscimol ændres den neuronale aktivitet i flere områder af hjernen, herunder cerebral cortex , hippocampus og cerebellum .
Mens muscimol normalt betragtes som en selektiv GABA(A)-agonist, er det også en delvis agonist ved GABA(A-rho- )-receptoren, og dermed er dets rækkevidde af virkninger resultatet af en kombineret virkning ved begge mål. [7 ]
Hos patienter med Huntingtons sygdom og kronisk skizofreni ham man fundet, at orale doser af muscimol medfører en stigning i både prolactin og væksthormon. [8 ]
Under en test, der involverede kaniner forbundet med et EEG-måleudstyr , medførte muscimol en tydeligt synkronisering af EEG- signalet. Dette er væsentligt forskelligt fra serotonergiske psykedelika , hvor de ændrede hjernebølge-mønstre generelt viser en desynkronisering.
I højere doser (2 mg / kg) vil EEG vise karakteristiske toppe.
En vis procentdel af muscimol bliver udskillet i urinen, og dette fænomen udnyttes af udøvere af den traditionelle entheogenic anvendelse af Amanita muscaria . [9 ]
Den psykoaktive dosis af muscimol er omkring 10-15 mg for en normal person. [10 ]
I "En vejledning til britiske Psilocybin-svampe" af Richard Cooper, udgivet i 1977, anbefales en mindre dosis på 8,5 mg og foreslår, at det er muligt at denne mængde kan være til stede i så lidt som 1 g tørret A. muscaria, men dette er ikke i overensstemmelse med de fleste andre rapporter, der tyder på at 5-10 g er nødvendig for at opnå denne mængde.
En korrekt dosis kan være vanskeligt at bestemme, fordi styrken varierer dramatisk fra den ene svamp til den næste.
eksternt billede 220px-Amanita_muscaria_3_vliegenzwammen_op_rij.jpg
Effekter
Mange af muscimol-virkningerne er i overensstemmelse med dets farmakologi som GABA(A)-receptor -agonist , der præsenterer mange virkninger, der betegnes depressivt eller beroligende – hypnotiske virkninger.
I modsætning til effektprofilen af beroligende stoffer generelt kan muscimol, som Z-stoffer , forårsage dissociative ændringer i opfattelsen. [11 ]
Jonathan Ottbeskriver virkningerne af Amanita pantherina nedenfor:
- Ca. 90 minutter efter indtagelse bemærkede jeg, at jeg oplevede ændringer i visuel opfattelse. Disse virkninger blev stærkere i løbet af den næste time eller få timer og var kendetegnet ved at livløse objekter syntes at blive levende, synsfeltet fik bølgende bevægelser som et Van Gogh maleri og mild forvrængning af størrelser, afstande og dybdeopfattelser. Lydmæssige hallucinationer var også fremtrædende – især effekten, der hedder ' anahata lyde ' af yoga, med at høre fine høje lyde som klokker og violinstrenge. [12 ]
Syntese
Muscimol kan fremstilles syntetisk fra lithium-acetylidet (?) afledt (?) af propargyl-chlorid .
Behandling med ethylchlorformiat giver ethyl-4-chlorotrolat, som kondenserer med hydroxylamin for at give chloromethylisoxazol. Vandfri ammoniak omdanner dette klorid til muscimol. [13 ]
Det samlede udbytte der er opnået ifølge litteraturen var 18,7%.
Toksicitet
LD50-tallet for 50% dødelighed for mus er 3,8 mg / kg sc, 2,5 mg / kg ip [14 ]
LD 50 i rotter er 4,5 mg / kg iv (intravenøst), 45 mg / kg oralt (via munden). [14 ]
Juridisk status
Muscimol betragtes som et forbudt stof i Australien (oktober 2015). [15 ]det betegnes som et stof ", der kan misbruges og at fremstilling, besiddelse, salg eller anvendelse bør være forbudt ved lov, undtagen når det kræves til medicinsk eller videnskabelig forskning eller til analytiske studier, undervisnings- eller uddannelsesformål med godkendelse af Commonwealth og / eller statslige eller territoriale sundhedsmyndigheder. " [15 ]
Se også
Muscimol From Wikipedia, the free encyclopedia
"Pantherine" redirects here. For the big cat subfamily, see Pantherinae.Muscimol||||= Muscimol chemical structure.svg
||Muscimol3d.png
Names
IUPAC name
5-(Aminomethyl)-isoxazol-3-ol
Identifiers
CAS Number
3D model (JSmol)
- 4116
Yes
ECHA InfoCard
100.018.574
IUPHAR/BPS
PubChem CID
InChI[show]
SMILES[show]
Properties[1]
Chemical 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 inmethanol
very soluble
Pharmacology
Legal status
- AU: S9 (Prohibited)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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?)
Infobox references
Muscimol (also known as agarin or pantherine) is the principal psychoactive constituent of Amanita muscaria and related species of mushroom. Muscimol is a potent, selective agonist for the GABAAreceptors and displays sedative-hypnotic, depressant and dissociative psychoactivity. This colorless or white solid is classified as an isoxazole.
==Contents==
[]
- 1Biochemistry
- 2Pharmacology
- 3Synthesis
- 4Toxicity
- 5Legal status
- 6See also
- 7References
- 8External links
Biochemistry
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.
Muscimol is produced in the mushrooms Amanita muscaria (fly agaric) 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
Muscimol is a potent GABAA agonist, activating the receptor for the brain's principal inhibitoryneurotransmitter, 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 normally thought of as a selective GABAA agonist, it is also a partial agonist at theGABAA-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 EEGtracing. 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 but this is not consistent with most other reports which suggest 5–10 g is necessary. A correct dose may be difficult to determine because potency varies dramatically from one mushroom to the next.
Effects
Many of muscimol's effects are consistent with its pharmacology as a GABAA receptor agonist, presenting many depressant or sedative–hypnoticeffects. Atypical of the effect profile of sedative drugs generally however, muscimol, like Z-drugs, can cause dissociative changes in perception.[citation needed][11] Jonathan Ott describes the effects of Amanita pantherina below:
- About 90 minutes after ingestion … I noticed that I was experiencing changes in visual perception. These effects became stronger over the next hour or some, and were characterized by sensing an 'alive quality' in inanimate objects, wavy motion in the visual field like a Van Gogh canvas … and mild distortion of size, distance and depth perception. Auditory hallucination were also prominent — especially the effect, called 'anahata sounds' of yoga, of hearing fine high-pitched sounds like bells and violin strings.[12]
Synthesis
It can be produced synthetically from the lithium acetylide derived from propargyl chloride. Treatment with ethyl chloroformate afford ethyl 4-chlorotetrolate, which condenses with hydroxylamine to give the chloromethylisoxazole. Anhydrous ammonia converts this chloride to muscimol.[13] The overall yield achieved in the literature was 18.7%.
Toxicity
The LD50 in mice is 3.8 mg/kg s.c, 2.5 mg/kg i.p.[14] The LD50 in rats is 4.5 mg/kg i.v, 45 mg/kg orally.[14]
Legal status
Australia
Muscimol is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).[15] A Schedule 9 substance is a substance "which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities."[15]
See also
References
- Jump up^ The Merck Index, 12th Edition
- Jump up^ 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.
- Jump up^ 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.
- Jump up^ 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.
- Jump up^ 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.
- Jump up^ 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.
- Jump up^ 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.
- Jump up^ 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.
- Jump up^ Goldstein A. (2001). //Addiction: From Biology to Drug Policy//. Oxford University Press. p. 228. ISBN 978-0-19-514664-6.
- Jump up^ "Erowid Psychoactive Amanitas Vault : Dosage".
- Jump up^ "Erowid Psychoactive Amanitas Vault : Effects".
- Jump up^ Ott, Jonathan (June 11, 2000). "Studies of Amanita: experience with Amanita muscaria (ID 366)". Erowid.org.
- Jump up^ McCarry, Brian E.; Savard, Marc (1981). "A facile synthesis of muscimol" (PDF). Tetrahedron Letters. 22 (51): 5153–5156.doi:10.1016/S0040-4039(01)92445-1.
- ^ Jump up to://**a**// //**b**// "Erowid Psychoactive Amanitas Vault : Chemistry".
- ^ Jump up to://**a**// //**b**// Poisons Standard October 2015https://www.comlaw.gov.au/Details/F2015L01534
Additional references
- Ito Y, Segawa K, Fukuda H; Segawa; Fukuda (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.; Chilton; Yamamura; Enna (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; 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; Neophytides; Chase; Frohman (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
[show]
Poisonous Amanita mushrooms
[show]
[show]
[show]
[show]
GABA metabolism and transport modulators
[show]Glutamate receptor modulators
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