Muscimol

347 °F decomposes (EPA, 1998)

175 °C (decomposes)

0.000294 [mmHg]

0.00001 [mm Hg] @25 °C

Crystals. Formerly used as a sedative and an anti-emetic. (EPA, 1998)

Solid; [Merck Index] White powder; [MSDSonline]

Danger

H300 (57.4%): Fatal if swallowed [Danger Acute toxicity, oral]

P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 68 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

This compound is a natural constituent of amanita mushrooms and is extremely toxic. It is a potent central nervous system depressant, and is believed to be responsible for most of the nervous system effects that result from eating this mushroom. The lowest toxic dose in humans has been reported at 109 mg/kg. (EPA, 1998)

Causes somnolence and rigidity in rat experiments; In humans (route not reported), caused sleep, hallucinations, nausea, and vomiting; [RTECS] A strong CNS depressant; A GABA agonist; [Merck Index] May cause irritation and CNS depression; May cause neurotoxic effects and convulsions; [MSDSonline]

P007; As stipulated in 40 CFR 261.33, when 5-aminomethyl)-3-isoxazolol, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 3(2H)-Isoxazolone, 5-(aminomethyl) is included on this list. Effective date 3/7/86; Sunset date: 2/19/95.

MUSCIMOL is an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides

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. Muscimol is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1000 lb or 454 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

Use dry chemical, carbon dioxide, water spray, or alcohol foam extinguishers. Poisonous gases including nitrogen oxides are produced in fire. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire, officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume, and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position.

Evacuate persons not wearing protective equipment from area of spill or leak until clean-up is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area after clean-up is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Contact your Department of Environmental Protection or your regional office of the federal EPA for specific recommendations. If employees are required to clean-up spills, they must be properly trained and equipped.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P007, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

If this chemical gets into the eyes, remove any contact lenses at once and irrigate immediately for at least 15 minutes, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin, remove contaminated clothing and wash immediately with soap and water. Speed in removing material from skin is of extreme importance. Seek medical attention immediately. If this chemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions) if breathing has stopped and CPR if heart action has stopped. Transfer promptly to a medical facility. when this chemical has been swallowed, get medical attention. Give large quantities of water and induce vomiting. Do not make an unconscious person vomit.

0.14 [mg/m3]

1.5 [mg/m3]

8.9 [mg/m3]

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)

Wear protective gloves and clothing to prevent any reasonable probability of skin contact. Safety equipment suppliers/manufacturers can provide recommendations on the most protective glove/clothing material for your operation. All protective clothing (suits, gloves, footwear, headgear) should be clean, available each day, and put on before work. Contact lenses should not be worn when working with this chemical. Wear dust-proof chemical goggles and face shield unless full facepiece respiratory protection is worn. Employees should wash immediately with soap when skin is wet or contaminated. Provide emergency showers and eyewash.

Muscimol was an antagonist of catalepsy in rats pretreated with high sc doses of perphenazine, haloperidol or reserpine and alpha-methyltyrosine.

In rats withdrawn from a chronic treatment with diazepam, the effects of muscimol, given into the III cerebral ventricle, on behavior and spectrum power of activity in the electrocorticogram were studied. In comparison to control rats which received only muscimol, in rats pretreated with diazepam (1 mg/kg/day for 30 consecutive days) the behavioral and electrocorticogram effects of muscimol were significantly reduced or abolished. In fact, in rats pretreated with diazepam a small dose (50 ng) of muscimol did not affect behavior or electrocorticogram activity, in contrast to control animals in which the same dose produced, after a period of locomotor stimulation and electrocorticogram desynchronization, typical and long-lasting behavioral sedation or sleep accompanied by a significant increase in total voltage power and in the lower frequency bands in the electrocorticogram. In addition, larger doses (100 and 200 ng) of muscimol, which in control rats produced a typical biphasic pattern of electrocorticogram and behavioral changes, ie an initial period of electrocorticogram desynchronization and behavioral stimulation, followed by a second period of behavioral and electrocorticogram sleep, in animals pretreated with diazepam, produced only an increase in total voltage power and in the lower frequency bands in the electrocorticogram resembling the effects of the small (50 ng) dose. The present experiments suggest that, after chronic stimulation of benzodiazepine receptors a decrease in sensitivity of receptors for gamma-aminobutyric acid occurs, since the effects of muscimol on behavior and spectrum power were significantly reduced or abolished.

In male Sprague-Dawley rats acute ethanol (1.0 and 2.0 g/kg) produced impairment of motor coordination and induced hypnosis (4.0 g/kg). Muscimol (1.25 mg/kg, ip) prior to ethanol administration enhanced motor impairment as measured by the aerial righting reflex. The rate of ethanol disappearance from the blood was unaltered by muscimol. Functional tolerance to the effect of ethanol on sleep time was produced by a 24 hr ethanol inhalation procedure. Animals tested 48 hr after ethanol inhalation exhibited a reduced sleep time from ethanol (4.0 g/kg). muscimol (1.75 mg/kg) was administered along with ethanol 48 hr following 1 day of ethanol inhalation. Although the animals exhibited tolerance to ethanol-induced hypnosis, they did not manifest tolerance to the effect of muscimol.

When given systemically to rats and humans, the drug of abuse 3,4 methylenedioxymethamphetamine (ecstasy, MDMA) elicits hyperthermia, hyperactivity, tachycardia, and hypertension. Chemically stimulating the dorsomedial hypothalamus (DMH), a brain region known to be involved in thermoregulation and in stress responses, causes similar effects. ...Therefore ... the hypothesis that neuronal activity in the DMH plays a role in MDMA-evoked sympathetic and behavioral responses /was tested/ by microinjecting artificial CSF or muscimol, a neuronal inhibitor, into the DMH prior to intravenous infusion of saline or MDMA in conscious rats. Core temperature, heart rate, mean arterial pressure and locomotor activity were recorded by telemetry every minute for 120 min. In rats previously microinjected with CSF, MDMA elicited significant increases from baseline in core temperature (+1.3+/-0.3 degrees C), locomotion (+50+/-6 counts/min), heart rate (+142+/-16 beats/min), and mean arterial pressure (+26+/-3 mmHg). Microinjecting muscimol into the DMH prior to MDMA prevented increases in core temperature and locomotion and attenuated increases in heart rate and mean arterial pressure. ...

For more Interactions (Complete) data for MUSCIMOL (22 total), please visit the HSDB record page.

Muscimol is a potent GABAA agonist, activating the receptor for the brain's major inhibitory neurotransmitter, GABA. Muscimol actually binds to the same binding 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. 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. However while muscimol is conventionally thought of as a selective GABAA agonist, it is also a potent partial agonist at the GABAC receptor, and so its effects profile results from a combined action at both targets. (L1142)

/HUMAN EXPOSURE STUDIES/ Human volunteers who ingested 7.5 mg muscimol or 50 to 90 mg ibotenic acid experienced within an hour symptoms that lasted 3 to 4 hours, with a few effects that lingered for about 10 hours and a hangover (headache) the next day. Subjects became inactive and experienced fatigue (the mushrooms also often cause an initial drowsiness, stupor or sleep), mild nausea and vomiting, muscle spasms in the extremities, various emotional changes (elation and excitement, or fear and withdrawal) and distorted perceptions of space and time, but only rarely hallucinations.

/SIGNS AND SYMPTOMS/ Intoxication produced by Amanita muscaria & related species arises from anticholinergic & hallucinogenic properties of variety of isoxazole deriv. symptoms incl irritability, restlessness, ataxia, hallucinations, & delirium. /Isoxazole deriv of Amanita muscaria & related species/

/SIGNS AND SYMPTOMS/ Amanita muscaria ... causes salivation, perspiration, nausea, bradycardia, and mydriasis. ... One to four mushrooms cause euphoria, a sense of lightness, colored visions, and visual hallucinations. Although muscarine is a constituent of these mushrooms, there is no constriction of the pupils in this poisoning. Instead there is mydriasis, which is thought to be a sympathetic effect from action on the CNS. Muscimol, and to a minor degree, ibotenic acid are believed to be the constituents largely responsible. No persistent ocular disturbances have been reported. /Amanita muscaria/

/SIGNS AND SYMPTOMS/ The /emotional change/ is sufficiently attractive to some that Amanita pantherina (which is more potent and more toxic than Amanita muscaria) is collected in the Pacific northwest and consumed (raw or cooked) for recreational purposes. Specimens of the fly agaric found in the eastern USA (especially the yellow variety) are said to be much less psychoactive than those collected in the west. Only rarely does Amanita muscaria anywhere contain enough muscarine to produce mild muscarnic effects; unknown irritants rather than muscarine are believed to be responsible for much of the nausea and vomiting. Deaths from these mushrooms are very rare, but as with some other types of fleshy fungi, children have been known to react in unexpected and dangerous ways (eg, convulsions). Adults rarely require drug treatment for muscimol-ibotenic acid poisoning. Atropine is said to make the delirium worse, and physostigmine is ineffective. /Amanita muscaria/

For more Human Toxicity Excerpts (Complete) data for MUSCIMOL (9 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Neurotoxicity/ Unilateral injection of muscimol into the substantia nigra of rats induced contralateral turning. Muscimol (10 ng) bilaterally injected induced behavioral stimulation. The behavioral stimulation seems dependent on a noncatecholaminergic neuronal pathway, probably present in substantia nigra with GABA (gamma-aminobutyric acid) as the mediating neurotransmitter.

/LABORATORY ANIMALS: Neurotoxicity/ Injection of muscimol (2 ng-2 ug) into the zona compacta of rats induced a C circling response with C body asymmetry. The rotations appeared to be unrelated to the dopaminergic pathway since they were antagonized by haloperidol.

/LABORATORY ANIMALS: Neurotoxicity/ 32 Male Sprague-Dawley rats were given microinjections of 6.25, 25, or 100 ng muscimol or saline into the median raphe nucleus, the dorsal raphe nucleus or the caudal portion of the ventral tegmental area. At least 3 days separated consecutive treatments. Muscimol elicited a dose dependent incr in locomotor activity in all three areas, as measured in infrared photocell boxes. All 3 doses of muscimol injected into the median raphe resulted in significant hyperactivity relative to saline baselines. In contrast, only the 100 ng dose produced significant effects in animals with cannulae in the dorsal raphe or caudal ventral tegmental area. No significant effects were seen with injections into the rostral portion of the ventral tegmental area or the midline pontine tegmentum caudal to the median raphe. Lower doses of muscimol were required to produce hyperactivity after injections into the median raphe than after injections into any of the other sites.

/LABORATORY ANIMALS: Neurotoxicity/ Ip injection of 0.5-5 mg/kg of muscimol produced hypomotility, catalepsy, & loss of righting reflex in mice. These effects were assoc with an initial brief fall followed by a more sustained incr in homovanillic acid & dihydroxyphenylacetic acid levels in brain, without changes in the dopamine concentration.

For more Non-Human Toxicity Excerpts (Complete) data for MUSCIMOL (48 total), please visit the HSDB record page.

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

P007; As stipulated in 40 CFR 261.33, when 5-aminomethyl)-3-isoxazolol, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 3(2H)-Isoxazolone, 5-(aminomethyl) is included on this list. Effective date 3/7/86; Sunset date: 2/19/95.

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. Muscimol is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1000 lb or 454 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

Molecular orbital calculations have been carried out on muscimol. The calculated properties of the molecules are related to the ability of muscimol to displace (3)H-labeled GABA (gamma-butyric acid) from the postsynaptic receptors of human cerebellum, & it is suggested that the dominant influence on the gabaergic activity is the pi-electron distribution in heterocyclic ring.

Previous electrophysiological studies have shown that the GABA(A)-receptor agonist muscimol is able to markedly increase the firing rate of rat nigral dopamine (DA) neurons. This action of the drug is paradoxical since local microiontophoretic application of the drug is associated with a clearcut inhibition of these neurons. ... An attempt was made to analyze the mechanism of this action of the drug /in this study/. Administration of muscimol (0.25-4.0 mg/kg, iv) was associated with a dose-dependent increase in firing rate as well as an increased bursting activity of the nigral DA neurons. Both these effects of muscimol were clearly antagonised by intravenous administration of the NMDA receptor antagonist MK 801(1 mg/kg) or by intracerebroventricular administration of the broad-spectrum excitatory amino acid receptor antagonist kynurenic acid. Furthermore, pretreatment with PNU 156561A (40 mg/kg, iv, 5-8 ht), a compound that raised endogenous kynurenic acid levels about 9 times, also clearly antagonized the actions of muscimol. Indeed, this treatment reversed the excitatory action of muscimol into an inhibitory effect on the nigral DA neurons. Here, /it is reported/ that the excitatory action of muscimol is mediated indirectly by release of glutamate.

In many neurons, increased rates of firing are accompanied by expression of the proto-oncoprotein Fos. ... Fos-like immunoreactivity in the mamillary body and the anterior thalamus /was examined/ following unilateral injections of ... muscimol into the ventral tegmental nucleus of Gudden (VTN). These injections resulted in a marked increase in Fos-like immunoreactivity ipsilaterally in both the medial mamillary nucleus and in its principle thalamic projection targets, the anteroventral and anteromedial thalamic nuclei. Since the projection from the VTN to the mamillary body has been shown to contain a substantial GABAergic component, these results are likely to reflect a disinhibition of mamillothalamic circuitry resulting from suppression of tonic inhibitory inputs arising in the VTN.

Isolated from Amanita muscaria; Used to study GABA receptors; [Merck Index] Used in studies of GABA-A receptors; [ChemIDplus]

MEDICATION: /SRP: FORMERLY USED AS/ SEDATIVE; ANTIEMETIC.

As a molecular probe to study GABA receptors.

A GABA A-agonist that causes rapid and reversible suppression of neurophysiological activity.

Muscimol is produced naturally in the mushrooms Amanita muscaria, Amanita pantherina, and Amanita gemmata, along with muscarine, muscazone, and ibotenic acid. (L1142)

3(2H)-Isoxazolone, 5-(aminomethyl)-: ACTIVE

Amanita pantherina and Amanita muscaria are commonly occurring mushrooms in Polish forests. They contain ibotenic acid and muscimol: the substances reacting with neurotransmitter receptors in central nervous system. The ingestion of these mushrooms produces a distinctive syndrome consisting of alternating phase of drowsiness and agitation with hallucinations, and sometimes with convulsions. ...

... structural identity with the insecticidal substances, pantherine and agarin.