Pyridoxamine Dihydrochloride - Vitamin B6 Derivative CAS 524-36-7 / Articles

Pyridoxamine Dihydrochloride (PADC) - Vitamin B6 Derivative for Metabolism, Glycation Inhibition, and Research

1. Introduction

Pyridoxamine dihydrochloride (CAS 524-36-7) is a stable, water-soluble salt form of pyridoxamine, one of the three natural forms of vitamin B6 (along with pyridoxine and pyridoxal). It is a hydrochloride salt obtained by combining pyridoxamine with two molar equivalents of hydrochloric acid. Pyridoxamine is a critical transient intermediate in catalysis of transamination reactions by vitamin B6-dependent enzymes. Unlike pyridoxine, pyridoxamine has an aminomethyl group at the 4-position of the pyridine ring, which endows it with unique chemical properties including the scavenging of free radical species and carbonyl species formed in sugar and lipid degradation, as well as chelation of metal ions that catalyze Amadori reactions.

2. Chemical and Physical Properties

Pyridoxamine dihydrochloride has the molecular formula C₈H₁₄Cl₂N₂O₂ and a molecular weight of 241.11 g/mol. It appears as a white to off-white crystalline powder with a melting point of approximately 224-227°C (decomposes). The compound is highly soluble in water (up to 100 mg/mL) and soluble in DMSO and methanol. It is stable under recommended storage conditions (typically –20°C in powder form), but is unstable in liquid media. The dihydrochloride salt form provides enhanced stability and handling compared to the free base.

3. Mechanism of Action and Biological Roles

Pyridoxamine dihydrochloride plays a central role in amino acid metabolism as a coenzyme form of vitamin B6. Its unique primary amine-containing structure enables it to act through multiple mechanisms:

Inhibition of advanced glycation end‑product (AGE) formation: Pyridoxamine traps reactive carbonyl intermediates formed during sugar and lipid degradation, thereby preventing the formation of AGEs. It inhibits post‑Amadori steps of the Maillard reaction and scavenges reactive carbonyl compounds.
Antioxidant activity: It quenches singlet oxygen (459.7 µM TE/µM) and inhibits the formation of malondialdehyde and 4‑hydroxynonenal adducts on proteins.
Metal chelation: Pyridoxamine acts as an iron chelator and also chelates other metal ions that catalyze Amadori reactions.
Nephroprotective effects: It blocks pathogenic oxidative pathways in the progression of diabetic nephropathy. Pyridoxamine dihydrochloride (Pyridorin™) has been investigated for its role in diabetic nephropathy, a serious complication of diabetes characterized by kidney damage.

4. Applications

Pyridoxamine dihydrochloride is used across multiple fields:

Pharmaceutical research: Investigated for diabetic nephropathy, diabetic retinopathy, hyperlipidemia, and kidney stone preventive therapies. It has been studied in clinical trials (PIONEER-CSG-17) for diabetic nephropathy.
Dietary supplements: Marketed as a dietary supplement, often as the hydrochloride salt. However, in the United States, the FDA ruled in January 2009 that pyridoxamine must be regulated as a pharmaceutical drug because it is the active ingredient in Pyridorin, a drug designed to prevent the progression of diabetic nephropathy.
Cell culture and biochemical research: Used as a component in cell culture media, enzymatic assays, and nutritional biochemistry.
Scientific studies: Employed in research on oxidative stress, reactive carbonyl species, and AGE inhibition.

5. Safety and Toxicology

Pyridoxamine dihydrochloride is generally considered safe at recommended doses. However, the following safety classifications apply:

Skin corrosion/irritation: Category 2 (H315 - Causes skin irritation)
Serious eye damage/irritation: Category 2 (H319 - Causes serious eye irritation)
Specific target organ toxicity (single exposure): Category 3 (H335 - May cause respiratory irritation)

The acute oral LD50 in rats is 7500 mg/kg. The compound is non-hazardous, non-toxic (at typical use levels), and non-flammable. Standard laboratory precautions should be observed: avoid contact with skin and eyes, use appropriate personal protective equipment (gloves, safety goggles), and work in a well-ventilated area.

6. Storage and Handling

Pyridoxamine dihydrochloride should be stored as a powder at –20°C (long-term) or 4°C (short-term). In solution, it should be stored at –80°C for up to 6 months or –20°C for up to 1 month. The compound should be protected from light and moisture, and stored in tightly sealed containers. Inert atmosphere storage is recommended.

7. Conclusion

Pyridoxamine dihydrochloride (PADC, CAS 524-36-7) is a versatile and bioavailable vitamin B6 derivative with important roles in amino acid metabolism, glycation inhibition, and oxidative stress protection. Its ability to inhibit advanced glycation end‑product formation, chelate metal ions, and scavenge reactive carbonyl species makes it a valuable compound in pharmaceutical research, dietary supplements, and cell culture applications. While generally safe at recommended doses, proper handling and storage are essential to maintain its stability and activity. Ongoing research continues to explore its therapeutic potential in diabetic complications and other oxidative stress‑related conditions.