Ademetionine Advanced Drug Monograph

Ademetionine Report

Name: Ademetionine Name (English): Ademetionine DrugBank ID: DB00118 Type: Small Molecule CAS Number: 29908-03-0

Uses: Ademetionine is used to treat various conditions, including:

• Liver diseases (e.g., cholestatic liver diseases, alcoholic fatty liver disease, non-alcoholic fatty liver disease, liver disease during pregnancy, liver conditions with reduced bile formation).
• Depression.
• Osteoarthritis (to reduce pain and swelling in the joints).
• Biliary cholangitis (an autoimmune disease of the liver).
• Excess cholesterol in bile and biliary and liver diseases caused by cystic fibrosis.
• Fibromyalgia symptoms.
• Nerve problems in people with AIDS.
• Sexual dysfunction in men with depression.

Mechanism of Action: Ademetionine (S-adenosylmethionine or SAMe) is a naturally occurring compound involved in several crucial biological processes:

• Methylation: It acts as a methyl donor in the transfer of a methyl group to other molecules like DNA, proteins, and lipids, which is essential for gene expression, protein function, and lipid metabolism.
• Trans-sulfuration: It participates in the synthesis of cysteine and glutathione, a vital antioxidant that protects liver cells from toxins and oxidative stress.
• Aminopropylation: It is a precursor in the synthesis of polyamines, which are involved in cellular growth and repair. In liver disease, ademetionine helps maintain glutathione levels, minimizing liver damage and preventing the accumulation of lipids associated with cirrhosis. In depression, it affects neurotransmitters like serotonin, which regulate mood. In osteoarthritis, it may stimulate cartilage production and reduce inflammation.

Pharmacokinetics: Absorption of ademetionine is affected by food and is best taken on an empty stomach, although taking it with food may minimize gastrointestinal side effects. Bioavailability following oral intake is low due to significant first-pass metabolism in the liver, where approximately 50% is metabolized.

Safety and Side Effects: Ademetionine is generally considered safe, but some side effects may occur, including:

• Gastrointestinal: Nausea, diarrhea, constipation, abdominal pain, abdominal discomfort.
• Neurological: Insomnia (difficulty sleeping), dizziness, headache, anxiety.
• General: Sweating.
• Rare: Allergic reactions (rash, itching, swelling, dizziness, difficulty breathing).

In patients with bipolar disorder, ademetionine may worsen symptoms of mania. High doses might potentially increase homocysteine levels, a risk factor for cardiovascular diseases.

Drug Interactions: Ademetionine can interact with several medications, including:

• Monoamine oxidase inhibitors (MAOIs): moclobemide, phenelzine, iproniazid, isocarboxazid, nialamide, tranylcypromine, selegiline.
• Antidepressants: bupropion, duloxetine, fluoxetine, sertraline, clomipramine, trazodone. Increased risk of serotonin syndrome may occur.
• Antiparkinsonian drugs: levodopa, carbidopa.
• Painkillers: tramadol, acetaminophen.
• Antidiabetic medications: May cause a severe reduction in blood sugar levels.
• Antacids containing aluminum: May decrease ademetionine absorption.

Caution is advised in patients with kidney disease, diabetes, and Parkinson's disease. It is recommended to consult a healthcare provider before taking ademetionine, especially during pregnancy and breastfeeding or when taking other medications.