Mebaal Mechanism of Action



Mega Lifesciences


Full Prescribing Info
Pharmacology: Methylcobalamin is 1 of the 2 active co-enzyme forms of vitamin B12. It is a cofactor to the enzyme methionine synthetase that function to transfer the methyl groups for the regeneration of methionine from homocysteine. Methylcobalamin is well transported to nerve cell organelles with a better transportation than cyanocobalamin, in animals. It is also pivotal to the synthesis of nucleic acids and proteins. Methylcobalamin promotes axonal regeneration. It normalizes the axonal skeletal protein transport in sciatic nerve cells from animal models with streptozotocin-induced diabetes mellitus. It exhibits neuropathologically and electrophysiologically inhibitory effects on nerve degeneration in neuropathies induced by drugs eg, adriamycin, acrylamide and vincristine models of axonal degeneration in mice and neuropathies in animals with spontaneous diabetes mellitus. Methylcobalamin promotes myelination (phospholipid synthesis). It acts as a methyl donor for the synthesis of lecithin, a major constituent of the medullary sheath lipid and increases myelination of neurons in animal tissue culture more than cobalamide does. Methylcobalamin restores delayed synaptic transmission and diminished neurotransmitters to normal. It restores end plate potential induction early by increasing nerve fiber excitability in crushed sciatic nerve. In addition, it also normalizes diminished brain tissue levels of acetylcholine in animals fed a choline-deficient diet. Methylcobalamin promotes the maturation and division of erythroblasts, thereby increasing erythrocyte production. It also brings about a rapid recovery of diminished red blood cell, hemoglobin and hematocrit in vitamin B12-deficient animals.
Pharmacokinetics: Absorption: Naturally found B12 dissociated from proteins in the stomach via the action of acid and the enzyme pepsin. The forms of B12 released by this process are methylcobalamin and adenosylcobalamin. All forms of B12 bind to proteins called haptocorrins or R proteins, which are secreted by the salivary glands and the gastric mucosa. The binding occurs in the stomach. Pancreatic proteases partially degrade the cobalamin-haptocorrin complexes in the small intestine where cobalamin that is released then binds to intrinsic factor (IF). Intrinsic factor is a glycoprotein, which is secreted by gastric parietal cells. The cobalamin-intrinsic factor complex is absorbed from the terminal ileum into the ileal enterocytes via a process that first requires the complex to bind to a receptor called cubilin. Total absorption increases with increased intake of the vitamin. However, the absorption efficacy of the vitamin decreases with increased dosage. Significantly, very large doses of methylcobalamin are absorbed with an absorption efficiency of about 1%. This occurs via passive diffusion even in the absence of the intrinsic factor. Thus, large doses may be given for the treatment of deficiency instead of using the parenteral route (usually, intramuscularly). There are now several studies confirming this. The absorption efficiency of methylcobalamin from foods is approximately 50%. Blood levels of patients indicate that sublingual methylcobalamin becomes available as early as 15 minutes after administration and is still elevated at 24 hrs. It is absorbed through the oral mucosa, which bypasses the need for it to bind with intrinsic factor in the stomach. About 80% of B12 in the plasma is in the methylcobalamin form.
Distribution: Methylcobalamin in the circulation is bound to the plasma proteins transcobalamin I (TCI), transcobalamin II (TCII) and transcobalamin III (TCIII). Approximately 80% of plasma B12 is bound to TCI. TCII is the principal B12-binding protein for the delivery of B12 to cells, via specific receptors for TCII. This B12-binding protein (TCII) is identical to the one that delivers B12 from the enterocytes to the portal circulation. Cobalamin is released from the cobalamin-IF complex and then binds to TCII that delivers it to the portal circulation. The portal circulation transports cobalamin to the liver which takes up about 50% of the vitamin; the remainder is transported to the other tissues of the body via the systemic circulation. The cobalamin-TCII complex is degraded intracellularly via lyosomal proteases to yield cobalamin (cyanocobalamin, methylcobalamin, adenosylcobalamin, hydroxocobalamin).
Metabolism: Cobalamin is metabolized to methylcobalamin in the cytosol and to adenosylcobalamin in the mitochondria. Methylcobalamin is the principal circulating form of cobalamin. Adenosylcobalamin comprises >70% of cobalamin in the liver, erythrocytes, kidney and brain. The total body content of cobalamin ranges from 2-3 mg, with approximately 50% of it residing in the liver.
Excretion: Methylcobalamin is secreted in the bile and reabsorbed via the enterohepatic circulation. Some of them, which are secreted in the bile, are excreted in the feces. Also, oral B12 that is not absorbed is excreted in the feces. Reabsorption of methylcobalamin via the enterohepatic circulation does not require the intrinsic factor. If the circulating level of B12 exceeds the B12-binding capacity of the blood, a situation that usually occurs following parenteral administration of the vitamin, the excess is excreted in the urine.
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