Pharmacology
DrugBankDescription
Methocarbamol was developed in the early 1950s as a treatment for muscle spasticity and the associated pain. It is a guaiacol glyceryl ether. Methocarbamol tablets and intramuscular injections are prescription medicines indicated in the United States as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. In Canada, methocarbamol can be sold as an over the counter oral medicine at a lower dose that may be combined with acetaminophen or ibuprofen. A combination product with acetylsalicylic acid and codeine is available in Canada by prescription. Methocarbamol was FDA approved on 16 July 1957.
Mechanism of Action
The mechanism of action of methocarbamol is thought to be dependant on its central nervous system depressant activity. This action may be mediated through blocking spinal polysynaptic reflexes, decreasing nerve transmission in spinal and supraspinal polysynaptic pathways, and prolonging the refractory period of muscle cells. Methocarbamol has been found to have no effect on contraction of muscle fibres, motor end plates, or nerve fibres.
Pharmacodynamics
Methacarbamol is a skeletal muscle relaxant with an unknown mechanism of action. Methacarbamol has been shown to block spinal polysynaptic reflexes, decrease nerve transmission in spinal and supraspinal polysynaptic pathways, and prolong the refractory period of muscle cells. Methocarbamol does not act as a local anesthetic upon injection. In animal studies, methocarbamol also prevents convulsions after electric shock.
Metabolism
Methocarbamol is metabolized in the liver by demethylation to 3-(2-hydroxyphenoxy)-1,2-propanediol-1-carbamate or hydroxylation to 3-(4-hydroxy-2-methoxyphenoxy)-1,2-propanediol-1-carbamate. Methocarbamol and its metabolites are conjugated through glucuronidation or sulfation.
Absorption
The time to maximum concentration is 1.1 hours for both healthy patients and those on hemodialysis. The maximum plasma concentration is 21.3mg/L for healthy patients and 28.7mg/L in hemodialysis patients. The area under the curve for healthy patients is 52.5mg/L\*hr and 87.1mg/L*hr in hemodialysis patients. AUC% based on terminal elimination half life is 2% for healthy patients and 4% for hemodialysis patients. Older studies report maximum plasma concentrations in 0.5 hours.
Toxicity
Overdose of methocarbamol may be associated with alcohol and other central nervous system depressants. Patients may experience nausea, drowsiness, blurred vision, hypotension, seizures, and coma. Treatment of overdose is generally through airway maintenance, monitoring urinary output, vital signs, and giving fluid intravenously if necessary. The oral LD50 in rats is 3576.2mg/kg. The FDA has classified methocarbamol as pregnancy category C. Animal and human studies have not been performed to determine the risks to a fetus, however fetal and congenital abnormalities have been reported. Methocarbamol is excreted in the milk of dogs, however it is unknown if this is also the case for humans. Caution should be exercised when taking methocarbamol while breastfeeding. Studies to assess the carcinogenicity, mutagenicity, or effects on fertility of methocarbamol have not been performed.
Indication
Methocarbamol tablets and intramuscular injections are indicated in the United States as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. Oral methocarbamol in America may be given up to 1500mg 4 times daily for 2-3 days. In Canada, methocarbamol containing oral formulations are sold over the counter for pain associated with muscle spasm. However, if these combination formulations include codeine, they are prescription only.
Half-life
The elimination half life is 1.14 hours in healthy subjects and 1.24 hours in subjects with renal insufficiency. Older studies report half lives of 1.6-2.15 hours.
Protein Binding
Methocarbamol is 46-50% protein bound in healthy patients and 47.3-48.9% protein bound in hemodialysis patients.
Elimination
In humans the majority of the dose is eliminated in the urine. In dogs, 88.85% of the dose is eliminated in urine and 2.14% in the feces. In rats, 84.5-92.5% of the dose is eliminated in the urine and 0-13.3% is eliminated in the feces.
Volume of Distribution
Volume of distribution data in humans is scarce. In horses, the volume of distribution is 515-942mL/kg at steady state or 724-1130mL/kg.
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Experience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
ErowidEffects aggregated from 15 experience reports (15 Erowid)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 2
Adverse Effects 3
Dose-Response Correlation
How effect frequency changes across dose levels
View data table
| Effect | Threshold (n=10) |
|---|---|
| Sedation | 30.0% |
| Motor Impairment | 30.0% |
| Stimulation | 30.0% |
| Headache | 30.0% |
| Euphoria | 20.0% |
| Body High | 20.0% |
| Nausea | 20.0% |
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 15 experience reports.
Limited tier coverage — most reports fall within the Threshold range. Effects at other dose levels may not be represented.
| Effect | Threshold (n=10) | |
|---|---|---|
| sedation | ||
| motor impairment | ||
| stimulation | ||
| headache | ||
| euphoria | ||
| body high | ||
| nausea |
Dosage Distribution
Dose distribution from experience reports
Real-World Dose Distribution
62K DosesFrom 19 individual dose entries
Oral (n=18)
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Redose Patterns
Redosing behavior across 12 reports