Background:
Parkinson s disease (PD) is a progressive neurodegenerative disorder that affects the brain cells that make the chemical dopamine. The primary medical treatment for PD has been to use medications to replace the dopamine that is missing from the brain. These medications can be effective at first, but after many years side effects and tolerance develop.
Surgery can treat basic PD symptoms and complications. Deep brain stimulation (DBS) offers a safer alternative as the therapy can be adjusted and reversed to minimize side effects and optimize beneficial effects. DBS treats the symptoms of PD but does not alter its course.
Infusions of neurochemicals or medications are another PD treatment method. NIH researchers have developed the technique of convection-enhanced delivery, which very precisely and consistently delivers infusions of many types into the brain. This project will allow researchers to infuse a medication, Muscimol, into the subthalamic region of the brain to see if it is as safe and effective as DBS.
Objectives:
To determine whether an infusion of Muscimol into the brain is safe and relieves the symptoms of Parkinson s disease.
To demonstrate that the infusion can be monitored with magnetic resonance imaging (MRI) using gadolinium.
Eligibility:
Patients 18 years of age and older who have Parkinson s disease and are preparing for bilateral subthalamic nucleus (STN) DBS surgery.
Patients will be divided into two groups. One group of patients will have a partial infusion of Muscimol into the STN, and the second group of patients will have complete infusion of Muscimol into the STN.
Design:
This study will begin 5 days before the patient undergoes bilateral subthalamic DBS surgery.
On Day 1 of the study, small thin tubes (microcatheters) will be inserted into the STN through the same incision and burr holes that are used for DBS. Two infusion studies of Muscimol will be performed on successive days: the first without PD medication (Day 3 of study) and the second with PD medication (Day 4 of study).
Each infusion will be monitored in the MRI suite, and researchers will perform clinical examinations of patients PD symptoms.
Following the study experiments, a second surgery will be performed to remove the microcatheters and to place DBS electrodes in the standard fashion.

Start Date02 Jun 2009

Sponsor / Collaborator

National Institute of Neurological Disorders & Stroke

NCT00005925

/ TerminatedPhase 1IIT

Trial of Intracerebral Infusion in Patients With Medically Intractable Epilepsy

This study will examine the safety and effectiveness of infusing a chemical called muscimol into the brain to control seizures in patients with intractable epilepsy (frequent seizures that persist despite therapy). Muscimol, which is similar to a naturally occurring brain chemical called GABA, has been shown to reduce seizures in rats. After the infusion study, patients will undergo a standard surgical procedure for controlling seizures.
Patients 18 years of age or older with intractable epilepsy may be eligible for this study. Before entering protocol 00-N-0158, candidates will be screened under protocol 01-N-0139, Evaluation and Treatment of Patients with Epilepsy, with a medical history, physical and neurologic examination, chest X-ray, electrocardiogram, blood and urine tests, electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI) of the head.
Patients enrolled in this study will have the following procedures:
Computerized tomography (CT) and magnetic resonance imaging (MRI) of the head to guide catheter/electrode placement (see #2).
Depth catheter/electrode placement into the presumed location of the seizure focus (the part of the brain where the seizures originate) - A small hole is drilled through the skull. A depth electrode with a hole in the center of the tubing is passed through the brain into the structures usually involved in intractable epilepsy. MRI will be done to check electrode placement. Video-EEG monitoring will continue for 5 days for this part of the study. Patients will be tested for their ability to understand and produce speech, see normally, move their arms and legs, distinguish sharp and dull objects, and put pegs in a pegboard. They will be questioned about headache, weakness, numbness or sleepiness. The electrode will be left in place for muscimol infusion (see #3).
Muscimol infusion - Into the seizure focus, patients will be given two infusions-one of saline (salt water) alone and one of muscimol diluted in saline. Each infusion will be given over a period of one-half to 5 1/2 days, infused at the rate of 0.1 ml (1/50th of a teaspoon) per hour. During the infusions video-EEG recordings will continue and patients will be interviewed and examined as described in #2 above).
Blood testing - About 2 tablespoons of blood will be drawn daily during the testing period and for the first 2 days after surgery (see #5).
Surgery - Temporal lobectomy or topectomy (removal of a small, specific area of brain tissue) is the standard surgical treatment for medically intractable epilepsy whose seizure focus is not in a critical brain region, such as an area that controls language, movement, or sensation. If the patient's seizures arise from one of these areas, an alternative procedure called multiple subpial transection will be offered. In this procedure, vertical cuts are made in the seizure focus to prevent neurons (nerve cells that transmit electrical impulses) in the focus from spreading the seizure to the rest of the brain.
Surgery follow-up - Patients will be monitored in the surgical intensive care unit for 24 to 48 hours and then in the NINDS nursing unit for 4 to 8 days before being discharged to home. Another visit in the NINDS outpatient clinic will be scheduled for 6-12 weeks after surgery.

Start Date23 Jun 2000

Sponsor / Collaborator

National Institute of Neurological Disorders & Stroke

100 Clinical Results associated with Muscimol

100 Translational Medicine associated with Muscimol

100 Patents (Medical) associated with Muscimol

5,705

Literatures (Medical) associated with Muscimol

01 Feb 2025·Behavioural Brain Research

Involvement of the serotonergic, GABAergic and glutamatergic systems of the rostral anterior cingulate cortex in the trait and state anxiety of adult male Wistar rats.

Article

Author: Franco, Heitor Santos ; Melo, João Eduardo Conceição ; Menezes, Edênia Cunha de ; Santos, José Ronaldo Dos ; Goes, Tiago Costa ; Marchioro, Murilo ; dos Santos, José Ronaldo ; Silva, Rodolfo Santos ; Oliveira e Silva, Ana Mara de ; de Menezes, Edênia Cunha ; Teixeira-Silva, Flavia ; Oliveira E Silva, Ana Mara de ; Almeida-Souza, Thiago Henrique ; Santos, Leandra Martins

Despite significant advancements to understand of the neural circuitry involved in anxiety, the neurobiology of trait anxiety remains unclear. The rostral anterior cingulate cortex (rACC) and various pathways have been implicated in its regulation, making it a key to trait anxiety. The present study aimed to investigate the role of these neurotransmitter systems in the rACC in trait anxiety. Since trait anxiety is known to modulate state anxiety, we further investigated this relationship. Specifically, in Experiment I, we used animals with high trait anxiety; in Experiment II, we used animals with low trait anxiety; and in Experiment III, we used animals with medium trait anxiety. Before each behavioral assessment, drugs that either increased or decreased serotonergic (Fluoxetine or WAY-100635), GABAergic (Muscimol or Bicuculline), and glutamatergic (NMDA or Ketamine) neurotransmission in the rACC were administered, along with their respective controls. Additionally, in Experiment IV, all animals from the previous experiments were subjected to the Elevated Plus Maze (EPM) and Hole board (HB) test and evaluated without taking into account their trait anxiety levels. The results of the present study showed that, in Exp I, the modulation of the serotonergic, GABAergic and glutamatergic systems in the rACC decreased trait anxiety in highly anxious rats, while by submitting the animals to HB, the administration of fluoxetine increased state anxiety. In Exp II, the modulation of all systems increased trait anxiety in rats with low trait anxiety, whereas, in HB, state anxiety levels were increased with the administration of NMDA. In Exp III, only the modulation of the glutamatergic system, with NMDA, increased both trait and state anxiety levels. However, none of the evaluated neurotransmitter systems altered the state anxiety modeled in the EPM. Overall, the results of the present study provide new insights into the role of the neurotransmitter systems in the rACC in the regulation of trait anxiety and state anxiety.

01 Jan 2025·Toxicon

Coma and confirmed epileptiform activity induced by Amanita pantherina poisoning

Article

Author: Eleftheriou, Georgios ; Giampreti, Andrea ; Butera, Raffaella ; Cirronis, Marco ; Gallo, Mariapina ; Faraoni, Lorella ; Bacis, Giuseppe ; Contessa, Gioia

Amanita pantherina poisoning is a rare event poorly described. The clinical picture is usually associated with the one of A. muscaria, but A. pantherina contains more muscimol causing more often coma. We describe a case of severe coma and seizures after A. pantherina ingestion. A woman of 56 years old was found at home unresponsive with miosis, clonic movements of four limbs, normal respiratory and cardiovascular functions and without cerebral ischemic symptoms. Her husband reported mushrooms ingestion 4 hours earlier that were picked up in the home garden and believed to be Macrolepiota procera. Unenhanced brain CT and cerebral CT angiography were normal. Blood tests were within normal range, including troponin I, creatine phosphokinase and lactate. Toxicological screening was negative for methadone, ecstasy, amphetamines, barbiturate, cannabinoids, cocaine, opioids and benzodiazepines. Suspecting ingestion of A. pantherina, gastrointestinal decontamination was done. Mycological examination of residual stems of the ingested mushrooms identified A. pantherina, and evaluation of photos of the same mushrooms growing in their garden confirmed the species. Electroencephalogram confirmed epileptiform activity and levetiracetam 3.000 mg/day was started. The patient was always hemodynamically stable but daily neurologic wake-up test highlighted the presence of agitation and clonic movements of the limbs up to the 7th day of hospitalization. Levetiracetam was tapered and stopped after two months based on neurological improvement. The patient recovered without sequelae. Amanita pantherina poisoning is a rare event and clinical picture of convulsions and coma often guides the diagnosis towards organic pathologies. The latter should be excluded first but an accurate anamnesis should also consider mushrooms consumption. Gastrointestinal decontamination may be the only therapy for reducing toxins absorption and clinical severity. Our patient had acute severe neurological effects lasted many days, but she completely recovered with intensive treatment and levetiracetam administration.

01 Jan 2025·Physiology & Behavior

GABAergic circuit interaction between central amygdala and bed nucleus of the stria terminalis in lipopolysaccharide-induced despair-like behavior

Article

Author: Seki, Kenjiro ; Takahashi, Haruna ; Aoto, Yuta ; Maeda, Sakura ; Tamura, Yuka ; Matsuki, Tohru

Hyperexcitability of central amygdala (CeA) induces depressive symptoms. The bed nucleus of the stria terminalis (BNST) receives GABAergic input from the CeA. However, it remains unclear whether the GABAergic neurons in the CeA projecting to BNST contribute to major depression. Here, we investigated the roles of GABAergic neurons in CeA and BNST in lipopolysaccharide (LPS)-induced despair-like behavior. We generated adeno-associated virus vectors (AAV) carrying shRNA against Gad67 to knock down GAD67 expression in CeA (Gad67-KD-CeA) or BNST (Gad67-KD-BNST) in C57BL/6J male mice. Despair-like behavior was assessed by tail suspension test (TST) 24 h after LPS administration. Saline-treated Gad67-KD-CeA mice exhibited longer immobility during TST than saline-treated AAV-injected control (AAV-Cont) mice. Although LPS increased immobility time in AAV-Cont mice, it did not affect immobility time in Gad67-KD-CeA mice. While LPS did not affect the immobility time in Gad67-KD-BNST mice, it increased immobility time in AAV-Cont mice. We injected GFP-expressing AAV with a Dlx promoter, specifically expressed in GABAergic neurons, into CeA, and FluoroGold, a retrograde neuronal tracer, into the BNST. GFP signals associated with CeA GABAergic neurons were detected in the BNST, contacting c-fos and GAD67-expressed cells following LPS. We detected the FluoroGold signals in GAD67- and c-fos-expressed neurons in the CeA after LPS administration. Bilateral intra-BNST injection of muscimol (2 pmol), a GABA_A receptor agonist, increased immobility time during TST. These findings suggest that LPS-decreased GABAergic activity in the CeA may lead to disinhibition of GABAergic interneurons in the BNST, resulting in GABA_A receptor activation and subsequently induces despair-like behavior.

News (Medical) associated with Muscimol

03 Jul 2024

·www.drugs.com

FDA Warns of 48 Illnesses, One Death Linked to Diamond Shruumz Edibles

WEDNESDAY, July 3, 2024 -- The U.S. Food and Drug Administration said Tuesday it is now investigating nearly 50 illnesses and one death that may be linked to eating Diamond Shruumz edibles. Of the 48 people in 24 states who said they got sick after eating the chocolate bars, cones and gummies, one patient has died and 27 have been hospitalized, the FDA noted in an updated health alert . Those who fell ill reported seizures, agitation, abnormal heart rates and loss of consciousness. The latest illness was reported Monday, FDA officials said. Last week, the company that makes the edibles issued a full recall of all its edibles after discovering high levels of a mushroom toxin in the products. The recall was issued "because such products contain muscimol, a chemical found in mushrooms of the genus amanita," California-based Prophet Premium Blends stated in its announcement. "Muscimol could be a potential cause of symptoms consistent with those observed in persons who became ill after eating Diamond Shruumz products," the company added. Reported symptoms include seizures, agitation, involuntary muscle contractions, loss of consciousness, confusion, sleepiness, nausea and vomiting, abnormal heart rates and high/low blood pressure. States with cases include Alabama, Arizona, California, Colorado, Georgia, Indiana, Iowa, Kentucky, Maryland, Minnesota, Missouri, Montana, Nevada, New Jersey, New York, North Carolina, Ohio, Pennsylvania, South Carolina and Tennessee. The FDA first advised consumers not to eat Diamond Shruumz microdosing chocolate bars two weeks ago, warning that people in four states had fallen ill. Some had to be intubated. The recalled products were distributed nationwide through retail stores and mail order. Back in late May, Prophet Premium received the first two complaints of people becoming ill after eating an entire chocolate bar. That prompted the company to conduct an analysis of its ingredients, which "showed higher than normal amounts of muscimol," the recall notice said. The company said it has stopped producing and distributing the Diamond Shruumz product line while it and the FDA continue to investigate the cause of the illnesses. Consumers who bought Diamond Shruumz products should stop using them and contact the company at 209-314-0881 or by email at info@diamondshruumz.com with their order number to get a refund. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

18 Jan 2024

·www.prnewswire.com

STNR Creations Launches Revolutionary Amanita Mushroom Gummies

Innovative Blend of Ancient Wisdom and Modern Science ORLANDO, Fla., Jan. 18, 2024 /PRNewswire/ -- STNR Creations, a trailblazer in hemp-derived and natural wellness products, proudly introduces its latest breakthrough: Energizing Amanita Mushroom Gummies, aptly named 'Not Your Grandma's Portobellos.' Expertly crafted, these gummies present a novel fusion of Amanita Muscaria with a special blend of cannabinoids, offering a safe, legal, and invigorating microdosing experience. This pioneering combination is designed to provide an unparalleled natural energy boost, opening new vistas in holistic health and well-being. Continue Reading Energizing and Relaxing Amanita Mushroom Gummies by STNR Creations Renowned for infusing innovation into the hemp industry with their 3 Gram Disposable vape device, STNR Creations now expands its horizons with the introduction of 'Not Your Grandma's Portobellos' Amanita Mushroom Gummies. These gummies blend the unique properties of Amanita Muscaria, a revered fungus, to create a natural, energizing supplement tailored for enthusiasts and busy professionals. Shaun Province, Vice President of Sales at STNR Creations, states, "Our 'Not Your Grandma's Portobellos' Amanita Mushroom Gummies represent our dedication to fusing ancient wisdom with modern innovation. We're thrilled to offer a product that responds to the increasing demand for natural wellness solutions, reflecting our commitment to quality, innovation, and customer satisfaction." What are Amanita Mushrooms? Characterized by their soft, white bodies and striking red caps with white spots, Amanita mushrooms (Amanita Muscaria) contain the psychoactive alkaloids muscarine and ibotenic acid. These convert into muscimol, which, unlike typical psychedelics like psilocybin that affect serotonin, interacts with GABA receptors. The 'Not Your Grandma's Amanita Mushroom Gummies' are more than just a product launch; they signify a movement towards redefining natural supplements. With a unique blend of Delta 9 extract and Amanita Muscaria or just the amazing fungus Amanita Muscaria with a touch of Cordyceps Kana, these gummies offer a distinct experience in relaxation and wellness, incorporating cannabinoids for added benefits. Each package contains six 500mg amanita mushroom extract blend gummies offering a mildly psychedelic experience. Company Information STNR Creations, a sanctuary for the hemp connoisseur, delivers unparalleled experiences in hemp's purest pleasures. Merging tradition with innovation, our product range extends from robust Delta 8 to pioneering THC-A, and now to innovative mushroom wellness solutions. We're not just crafting products; we're cultivating trust and fostering a lifestyle of excellence and diversity in the natural wellness sphere. All STNR Creations products are proudly made in the United States, using the highest quality ingredients and rigorously tested for potency and purity by third-party laboratories. To learn more or to submit a wholesale inquiry, please contact the STNR Creations sales team via email at [email protected] or by phone at 855-STNR-779 (855-786-7779). These groundbreaking products are currently available for retail purchase at . Media Contact: Jeffrey Donahue 855-786-7779 [email protected] SOURCE STNR Creations LLC

14 Jun 2023

·www.prnewswire.com

Iconic U.S. Mushroom Supplement Company VidaCap Ventures Into the World of Amanita Muscaria

SCOTTSDALE, Ariz, June 14, 2023 /PRNewswire/ -- Popular American mushroom supplements company VidaCap has announced the brand will be launching a new line of products made from the extract of Amanita muscaria mushrooms. Long known for their therapeutic single dose mushroom extract capsules, this will be VidaCap's first foray into the world of Amanita Muscaria Gummies. Amanita muscaria, also known as the 'fly agaric' mushroom, has been prized for millenia in Eastern culture thanks to its therapeutic action and mind-altering effects. Historically, extract from the mushroom has been used during ceremonial rituals, spiritual awakenings, and in a variety of therapeutic Eastern medicine practices. However, VidaCap makes it clear that these mushrooms do not contain psilocybin - the active ingredient in 'magic mushrooms.' Rather, most of the effects of Amanita muscaria mushrooms are believed to come from the action of muscimol - a GABA agonist that produces a range of relaxing, almost hypnotic effects. In fact, so calming and relaxing are the effects of the mushroom that famous American author R. Gordon Wasson once suggested that Amanita was the soma that is talked about in the Rigveda of India. Of course, these claims have never been substantiated as it is unclear what exactly soma is, as described in the Rigveda. VidaCap's Amanita mushroom products will come in the form of gummies, which is a deviation from the popular single dose capsules the brand has become known for. "We couldn't be more excited or proud to finally be venturing into the world of Amanita," said VidaCap founder Jeff Yauck. "This is truly a fascinating mushroom, and our team has spent years waiting for this day - we're thrilled to be one of the first companies in the US to bring these products to the mainstream market." Unlike psilocybin-containing mushrooms, which are illegal in the US, Amanita mushrooms are available for order on the official VidaCap USA website. While the effects of Amanita muscaria can vary wildly depending on dose (and from person to person), a typical Amanita experience is one filled with immense joy, peacefulness, calm, and increased mindfulness. Users often feel a great sense of balance and harmony, without the strong visuals associated with so-called 'magic mushrooms.' To learn more about VidaCap's new Amanita muscaria mushroom products, visit the brand's official website at VidaCap.com. Contact: Jeff Yauck [email protected]com +1 (909) 640-3612 SOURCE VidaCap

100 Deals associated with Muscimol

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KEGG	Wiki	ATC	Drug Bank
-	Muscimol	-	DB12458

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Phase 1	-	National Institute of Neurological Disorders & Stroke	02 Jun 2009
Drug Resistant Epilepsy	Phase 1	US	National Institute of Neurological Disorders & Stroke	23 Jun 2000

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2004	Not Applicable	-	-	Muscimol-biotin	muvirdwhss(kqglxjnznl) = isdsaxckub zaargcikee (bwistbrcsf ) View more	-	01 May 2004
				Muscimol	tijkbosmnv(rqquhkikpo) = tmzwyceswp wxlmpwtdfm (okaojfhqse )
SFN2003	Not Applicable	-	-	Muscimol	(xgnmrovwux) = mppuqkfwnp lizcknmjus (dirzsomdly )	-	09 Nov 2003
				Dextromethorphan	(xgnmrovwux) = xqgzwcgivq lizcknmjus (dirzsomdly )
SFN2001	Not Applicable	Sleep	-	Muscimol	zwxslbtgcc(htcwoatqks) = A small decrease in PGO density during AS was observed following the injection of muscimol cqcxucegal (cdylojvzyk )	-	13 Nov 2001

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