Methycobal is a mecobalamin
preparation developed by Eisai Co., Ltd. as a treatment for peripheral
neuropathies. Methycobal contains mecobalamin, a vitamin B12-coenzyme that
occurs in the blood and the cerebrospinal fluid; it is taken up by nerve
tissues more actively and extensively than other homologues of vitamin B12.
Biochemically, Methycobal accelerates the metabolic pathways of nucleic
acids, proteins and lipids through its involvement in the transmethylation
reaction; thus, it exerts a repairing effect on injured nerve tissues.
Clinically, Methycobal is the first pharmaceutical product that has been
shown, by double-blind clinical studies, to be effective and useful for the
treatment of numbness, pain, and paralysis due to peripheral neuropathies
such as diabetic neuropathy and polyneuritis.
Each tablet contains 500 µg of mecobalamin.
Dosage and Administration
The usual daily dose for adults is 3 tablets, equivalent to a total of 1,500
µg of mecobalamin, administered orally in 3 divided doses.
The dose should he adjusted according to the age of patient and severity of
Methycobal should not be administered for extensive periods (months) to
patients who show no clinical response.
2) Adverse reactions
Symptoms such as anorexia, nausea or diarrhea may infrequently occur.
Skin rash may rarely occur.
Prolonged use of larger doses of Methycobal is not recommended for patients
whose occupation requires handling mercury or its compounds.
1. Promotion of the metabolism of nucleic acids, proteins and lipids
Experiments with a brain-derived cell line from albino rats have shown that
mecobalamin, by acting as a coenzyme in the formation of methionine from
homocysteine, is involved in the synthesis of thymidylate from deoxyundylate,
and promotes the synthesis of DNA and RNA. It has also been demonstrated. in
experiments using neuroglia, that mecobalamin enhances the formation of
lecithin, a major component of the myelin sheath.
2. Extensive uptake by nerve tissues and improvement of metabolic
Mecobalamin, a methylated form of vitamin B12 (CH3-B12) that occurs in high
concentrations in the blood and the cerebrospinal fluid, has been observed
in rats to be taken up into nerve cell organelles more actively and
extensively than CN-B12. Experimentation using sciatic nerve cells from
rats with experimental diabetes has also demonstrated that Mecobalamin helps
maintain axonal function by promoting the synthesis of structural proteins
and by normalizing the transport velocity of these proteins.
3. Repair of nerve injury
Mecobalamin has been demonstrated, by neuropathological and
electrophysiological studies, to inhibit nerve fiber degeneration in rats
and rabbits with neuropathy induced by drugs such as Adriamycin and
Vincristine or with Streptozotocin - induced diabetes. The effects of
mecobalamin were also studied in guinea pig models with compression-induced
facial palsy. The recovery process was evaluated using examinations of the
blink reflex, evoked electromyograms, and histological observations. Mecobalamin
was found to be as effective as steroids in accelerating the repair of
injured nerve tissue.
1. Single dose administration
After oral administration of single doses of 120 µg or 1,500 µg of mecobalamin
to healthy adult subjects, dose-dependent peak plasma
concentrations were reached in 3 hours in both cases. The half-life,
increase of plasma concentration of total B12, and ^AUC12 were as shown below.
Of the cumulative amount of total B12 recovered in the urine by 24 hours
after oral administration, 40 to 80 percent was excreted within the first 8
2.8 ± 0.2
3.6 ± 0.5
743 ± 47
972 ± 55
37 ± 15
255 ± 51
5.1 ± 2.1
36.0 ± 7.9
168 ± 58
2033 ± 510
*1 Calculated by the trapezoidal
formula from the increment in observed 12-hour values, as compared to
*2 Calculated from the average of
24-48 hour values.
Mean ± Standard error.
2. Repeated dose administration
Plasma concentrations of total B12 were measured in healthy subjects given
an oral daily dose of 1,500 µg of Methycobal for 12 consecutive weeks.
Plasma B12 concentrations were also monitored in the same
patients for the 4 weeks immediately following the last administration. The
plasma concentration increased for the first 4 weeks after administration,
reaching a value twice as high as the initial concentration. Thereafter,
there was a gradual increase which reached a peak at approximately 280% of
the initial value at the 12th week of dosing. The plasma concentration
declined after the last administration (12 weeks), but was still
approximately 180% of the initial level 4 weeks after the last