Mebaal Plus-150 Mechanism of Action

Pharmacology: Pharmacodynamics: Methylcobalamin: Synthesis of the myelin coating of peripheral nerves requires adequate availability of vitamin B₁₂.
Myelin is a lipoprotein and Methylcobalamin participates in the synthesis of phospholipid and the protein components.
Lipid synthesis: Methylcobalamin supplies necessary methyl group for phospholipid (also referred to as lecithin, the main constituent of medullary sheath lipids) manufacturing.
Protein synthesis: Methylcobalamin also upregulates gene transcription resulting in protein synthesis stimulation.
Even in Wallerian degeneration, wherein the nerve is crushed, Methylcobalamin has ability to regenerate it and improve conduction.
MEBAAL Plus provides vitamin B₁₂ in its active form as Methylcobalamin (Mecobalamin).
Supplementing the active form of vitamin B₁₂ namely Methylcobalamin is always advantageous since it ensures adequate direct availability of vitamin B₁₂ without depending on the body for conversion from cyanocobalamin (a form of vitamin B₁₂ usually taken) to Methylcobalamin. Both vitamin B₁₂ and folic acid are required for synthesis of deoxyribonucleic acid (DNA). Folic acid exists as methyl folate in body. A vitamin B₁₂ - containing enzyme removes a methyl group from the latter thereby converting methyl folate to tetrahydrofolicacid (THFA). It is THFA that is involved in DNA synthesis.
Pregabalin: Neuropathic pain generally does not respond to treatment with opioid or nonsteroidal anti-inflammatory drugs NSAIDs. Data from clinical studies have demonstrated that Pregabalin shares similar analgesic effectiveness as gabapentin for neuropathy pain. Besides, Pregabalin is also effective for epilepsy and fibromyalgia.
Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues.
Although the mechanism of action of Pregabalin is unknown, binding to the alpha2-delta subunit may be involved in MEBAAL Plus's antinociceptive and antiseizure effects. Pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function.
While Pregabalin is a structural derivative of the inhibitory neurotransmitter gammaaminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses nor does it alter brain GABA concentration or have acute effects on GABA uptake or degradation. However, Pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity, it is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin or noradrenaline reuptake.
Pharmacokinetics: Methylcobalamin: Methylcobalamin and cyanocobalamin are similarly absorbed from the gastrointestinal (GI) tract. The cobalamine are bound to specialized transport proteins intrinsic factor (of stomach), which facilitates their entry into the cells lining the intestinal mucosa. Entry in the physiological conditions occurs only via the ileum. Inside the body, Methylcobalamin is transported into all other cells only when bound to another transport protein, transcobalamin II.
The C_max of B₁₂ is reached in 3 hours. Following single dose intake of 1500 mcg, the C_max obtained is 972 pg/ml. In the liver significantly more cobalamin accumulates following methylcobalamin intake than cyanocobalamin. 40-80% of total B₁₂ is excreted in urine in 24 hours. Human Methylcobalamin urinary excretion is about one-third that of a similar dose of cyanocobalamin, indicating substantial greater tissue retention.
Pregabalin: Pregabalin is well absorbed after oral administration of MEBAAL Plus, and the rate of absorption is decreased when given with food, resulting in a decrease in maximum blood concentrations (C_max) of approximately 25% to 30% and an increase in times taken for Cmax (T_max) to approximately 3 hours.
However, administration of Pregabalin with food has no clinically relevant effect on the total absorption of Pregabalin. Therefore, MEBAAL Plus can be taken with or without food.
The oral bioavailability of Pregabalin is 90% and is independent of dose. Following repeated administration, steady state is achieved within 24 to 48 hours.
Pregabalin does not bind to plasma proteins. The apparent volume of distribution of Pregabalin following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for system L transporter which is responsible for the transport of large amino acids across the blood brain barrier. In addition to crossing the blood-brain barrier, Pregabalin also crosses the placenta and is present in the milk during lactation.
Pregabalin undergoes negligible metabolism in humans. Following an oral dose of MEBAAL Plus, approximately 90% of it is recovered in the urine as unchanged Pregabalin. The N-methylated derivative, the major metabolite of Pregabalin found in urine, accounts for 0.9% of the dose. Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance is estimated to be 67.0 to 80.9 ml/min in young healthy subjects. Because Pregabalin is not bound to plasma proteins this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to creatinine clearance.