Metadoxine

Key takeaways

Metadoxine belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Metadoxine to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Metadoxine from memory before moving on to harder problems.

Reference excerpt

Metadoxine, also known as pyridoxine-pyrrolidone carboxylate, is a drug used to treat chronic and acute alcohol intoxication. Metadoxine accelerates alcohol clearance from the blood. Metadoxine is an ion pair salt of pyridoxine and pyrrolidone carboxylate (PCA). Pyridoxine (vitamin B6) is a precursor of coenzymes including pyridoxal 5’-phosphate (PLP), which accelerates the metabolic degradation of ethanol and prevents adenosine triphosphate (ATP) inactivation by acetaldehyde. Pyridoxal phosphate dependent enzymes also play a role in the biosynthesis of four important neurotransmitters: serotonin (5-HT), epinephrine, norepinephrine and GABA: see vitamin B6 functions.

Medical uses As a treatment for alcohol intoxication and liver disease, metadoxine is typically given intravenously as immediate release formulation.

Acute alcohol intoxication In clinical studies, metadoxine has been reported to reduce the half-life of ethanol in healthy volunteers and in acutely intoxicated patients; to accelerate the metabolism of alcohol and acetaldehyde into less toxic higher ketones and to improve their urinary clearance; to restore laboratory variables such as alcohol, ammonia, γ-GT, and alanine aminotransferase; and to improve clinical symptoms of alcohol intoxication, including psychomotor agitation, depression, aggressiveness, and equilibrium disorders. There is also evidence that metadoxine has an effect on reducing craving for alcohol. Data from clinical studies also support an effect of metadoxine on reducing indices of liver cell necrosis and fat accumulation in alcoholic fatty liver.

Liver disease Metadoxine may block the differentiation step of preadipocytes by inhibiting CREB phosphorylation and binding to the cAMP response element, thereby repressing CCAAT/enhancer-binding protein b during hormone-induced adipogenesis. Metadoxine, when given in an immediate release form in doses from 300 mg twice a day to 500 mg three times a day of up to 3 months, has been shown to improve biochemical indices of liver function as well as reduce ultrasonic evidence of fatty liver disease.

Pharmacology

Mechanism of action Metadoxine is a selective antagonist of the serotonin receptor subtype 5-HT2B and displays high affinity to the gamma-aminobutyric acid (GABA) transporter. In vitro enzymatic assay revealed that metadoxine reduced the activity of the GABA transaminase enzyme, responsible for the degradation of GABA. Electrophysiological studies also showed that metadoxine increased inhibitory GABAergic synaptic transmission via a presynaptic effect. As it does not affect dopamine, norepinephrine or serotonin levels, metadoxine displays a novel mechanism of action as a monoamine-independent GABA modulator. In animal studies, metadoxine increased the activity of acetaldehyde dehydrogenase enzyme, prevented the decrease in alcohol dehydrogenase activity in chronic ethanol-fed rats, accelerated plasma and urinary clearance of ethanol, inhibited the increase of fatty acid esters in the liver of ethanol-treated rats, prevented the formation of fatty liver in rats exposed to a dose of ethanol sufficient to induce fatty liver, increased glutathione levels in the hepatocytes of acutely and chronically alcohol-intoxicated rats, prevented glutathione depletion, lipid peroxidation damage, collagen deposition, and TNF-α secretions induced by alcohol and acetaldehyde in hepatocytes and hepatic stellate cells.

History Metadoxine is predominantly used as metadoxine immediate release formulation in developing nations for acute alcohol intoxication and chronic alcoholic liver disease. Alternate names include:

Abrixone (Eurodrug, Mexico) Alcotel (Il Yang, South Korea) Ganxin (Qidu Pharmaceutical, China) Metadoxil (Baldacci, Brazil; Baldacci Georgia; Baldacci, Italy; Baldacci, Lithuania; CSC, Russian Federation; Eurodrug, Colombia; Eurodrug, Hungary; Eurodrug, Thailand) NEXT LABS (India) Alkodez ІС (Ukraine) Viboliv (Dr. Reddy's, India) EXTOL (Next Labs, India) Xin Li De (Zhenyuan Pharm, China)

Research

ADHD Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders of childhood and is among the most prevalent chronic health conditions affecting school-aged children. The core symptoms of ADHD include inattention, difficulty staying focused, hyperactivity, and impulsivity. Metadoxine exhibited cognition enhancing effect in the rat social recognition animal model. An extended release formulation of metadoxine (MDX), combining immediate and slow release formulations of metadoxine into a single oral dose, was developed to extend the half-life of the drug and to allow for the use of MDX in indications that require a longer therapeutic window, such as cognitive impairment-related disorders. MDX has demonstrated significant and clinically meaningful improvements in multiple measures of cognition, ADHD symptoms, and quality of life, across multiple studies of adults with ADHD. Several Phase II ADHD studies demonstrated a consistent signal of efficacy reaching statistical significance, as measured by neuropsychological testing (such as the computerized Test of Variables of Attention (TOVA) in acute settings) and clinical scales (in chronic administration studies), with no treatment-related serious adverse events or major differences in adverse events profiles between drug and placebo groups. The most common adverse events were nausea, fatigue, and headache. A phase 3 study in 300 adults with ADHD was completed in 2014. Alcobra Ltd., which was conducting the Phase III trial announced on January 17, 2017 that the drug had failed the trial. The failure announcement came a week after Alcobra won FDA agreement to review data collected to date in the MEASURE study and consider it in a future NDA submission of MDX for ADHD. The FDA also agreed to change a full clinical hold for the trial to a partial clinical hold pending review and approval of the company's proposed protocol for a 6-month, Phase I study to assess the potential relevance of adverse findings observed in long-term animal studies of metadoxine in relation to human exposure, Alcobra said.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Metadoxine

Start with the simplest possible case. Write down what Metadoxine claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Metadoxine before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Metadoxine ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Metadoxine

In research: Metadoxine appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Metadoxine in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Metadoxine is common in secondary-school and first-year university syllabi. It links to neighbouring topics 5-HT2B antagonists, Alcohol abuse, Drugs acting on the nervous system, so understanding it makes those chapters shorter.
In everyday life: Look for Metadoxine outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Metadoxine in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Metadoxine means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Metadoxine out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Metadoxine in simple terms?

Metadoxine, also known as pyridoxine-pyrrolidone carboxylate, is a drug used to treat chronic and acute alcohol intoxication. Metadoxine accelerates alcohol clearance from the blood.

Why does Metadoxine matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Metadoxine?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Metadoxine.