[+work in progress] [Zolpidem off-label Miracles for the Sick - Myth or Not ?]

[Chip (OP)]

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sources: multiple and mixed, sorry about that (Wiki etc.)

The imidazopyridines are GABAA receptor agonists

It is thought that the primary mode of action utilized by Z-drugs is selective, and carries a high affinity for the a1 hypnotic-inducing site on the benzodiazepine subunit within the GABAA receptor.

video source: HAMILTON'S PHARMACOPEIA  S1 • E15 • Medical Miracles with Ambien

https://www.ncbi.nlm.nih.gov/pubmed/28534652

source of the quote below: VICE

Zolpidem tartrate, or Ambien, has been prescribed to millions of insomniacs internationally, yet those who use the drug to ensure a good night's sleep are seldom aware it also possesses the ability to normalize functioning in certain types of damaged neurons, a phenomenon called "the Ambien effect." The first awakening occurred in 1999 when a man who had spent three years in a persistent vegetative state spontaneously regained consciousness after ingesting a 10mg tablet. Since then, hundreds of patients have experienced miraculous recoveries from traumatic brain injury using Ambien. Hamilton Morris travels from South Africa, where the Ambien effect was first discovered, to England to interview a physician on the cutting edge of Ambien research, and then to Florida to meet a voice-over artist who depends on Ambien to speak.

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Recently proton pump inhibitors, aromatase inhibitors, NSAIDs and other classes of drugs in this class have been developed as well. Despite usually being

similar to them in effect, they are not chemically related to benzodiazepines. As such, GABAA-agonizing imidazopyridines, pyrazolopyrimidines, and

cyclopyrrones are sometimes grouped together and referred to as "nonbenzodiazepines." Imidazopyridines include:

Anxiolytics, sedatives and hypnotics (GABAA receptor positive allosteric modulators):

Imidazo[1,2-a]pyridines:

Alpidem (original brand name Ananxyl)—an anxiolytic that was withdrawn from the market worldwide in 1995 due to hepatotoxicity.

DS-1—a GABAA receptor positive allosteric modulator selective for the a4ß3d subtype, which is not targeted by other GABAergics such as benzodiazepines or

other nonbenzodiazepines.
 
Necopidem—an anxiolytic. It has not found clinical use.

Saripidem—a sedative and anxiolytic. It is not used clinically.

TP-003—a subtype-selective partial agonist at GABAA receptors, binding to GABAA receptor complexes bearing either a2, a3 or a5 subunits, but only showing

significant efficacy at a3.



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Zolpidem^Wiki (original brand name Ambien)—a widely used hypnotic.

* it is a Imidazo[1,2-a]pyridines (a salt or ester of tartaric acid.

A Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one methine group (=CH−)

replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-soluble liquid with a distinctive, unpleasant fish-like smell.


Tartaric acid^Wiki is a white, crystalline organic acid that occurs naturally in many fruits, most notably in grapes, but also mainly in bananas, tamarinds, citrus and grapes.

Tartaric is an alpha-hydroxy-carboxylic acid, is diprotic and aldaric in acid characteristics, and is a dihydroxyl derivative of succinic acid.

citrus.Its salt, potassium bitartrate, commonly known as cream of tartar, develops naturally in the process of winemaking.

NOTE the Potassium component + it may be significant as is the "tart" nature of it's other sources.


It decreases the time to sleep onset by about 15 minutes and at larger doses helps people stay asleep longer (i assert that this causes some degree of amnesia yet it is a paradox - it also UNhandicaps some people and their wide awake !

IT IS CLAIMED THAT: Twelve months of nightly zolpidem does not lead to rebound insomnia or withdrawal symptoms: a prospective placebo-controlled study









 
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Imidazo[4,5-c]pyridines:

Bamaluzole—a GABAA receptor-agonizing anticonvulsant that was never marketed.
 
Antipsychotics:
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Imidazo[1,2-a]pyridines:
Mosapramine (brand name ????, Cremin)—an atypical antipsychotic used in Japan.
 
Drugs used for peptic ulcer disease (PUD), GERD and gastroprokinetic agents (motility stimulants):

Imidazo[1,2-a]pyridines:

CJ-033466—an experimental gastroprokinetic acting as a selective 5-HT4 serotonin receptor partial agonist.
Zolimidine—a gastroprotective agent.
 
Linaprazan—a potassium-competitive acid blocker which demonstrated similar efficacy as esomeprazole in healing and controlling symptoms of GERD patients

with erosive esophagitis.
 
SCH28080—the prototypical potassium-competitive acid blocker which has not found clinical use because of liver toxicity in animal trials and elevated liver

enzyme activity in the serum of human volunteers.
 
Imidazo[4,5-b]pyridines:

Tenatoprazole—it blocks the gastric proton pump leading to decline of gastric acid production.
NSAIDs, analgesics and antimigraine drugs:

Imidazo[1,2-a]pyridines:

Miroprofen—a derivative of propionic acid.

Imidazo[4,5-b]pyridines:

Telcagepant—a calcitonin gene-related peptide receptor antagonist which was in clinical trials as a remedy for migraine. Its development was terminated.

Drugs acting on the cardiovascular system:

Imidazo[1,2-a]pyridines:
Olprinone (loprinone)—a cardiac stimulant.
Drugs for treatment of bone diseases:

Imidazo[1,2-a]pyridines:
Minodronic acid (brand names Bonoteo, Recalbon)—a third-generation bisphosphonate used for the treatment of osteoporosis.
Antineoplastic agents:

Imidazo[1,5-a]pyridines:
Fadrozole (brand name Afema)—an aromatase inhibitor.
Imidazo[4,5-c]pyridines:
3-Deazaneplanocin A—an S-adenosyl-L-homocysteine synthesis inhibitor and histone methyltransferase EZH2 inhibitor.

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follow up later:

The effects of repeated zolpidem treatment on tolerance, withdrawal-like symptoms, and GABAA receptor mRNAs profile expression in mice: comparison with diazepam.

Drug-related Sleep Stage Changes: Functional Significance and Clinical Relevance

source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041980/

On the other hand, the non-benzodiazepine BzRAs do not appear to consistently alter sleep stages (8). In one study of healthy 21–35 yr old normals, zolpidem 0–20 mg did not affect stage 1 or stage 3–4 (9). The high dose reduced REM sleep. Zopiclone 0–15 mg in middle-age insomniacs reduced stage 1 from 12% to 8% (10).

[Chip (OP)]

Could it work for Locked In Syndrome (psuedocoma) ?

More on altering states of consciousness >

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951253/