Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Methocarbamol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Methocarbamol: evaluation of reinforcing and discriminative stimulus effects.

The behavioural effects of methocarbamol, a centrally acting muscle relaxant, were assessed using self-injection procedures in baboons and drug discrimination procedures in baboons and rats. The ability of methocarbamol to maintain self-injection was examined using a drug substitution procedure. Responding was maintained initially by cocaine delivery (0.32mg/kg/injection, i.v.). Each drug injection was followed by a 3-h timeout allowing a maximum of eight injections per day. Methocarbamol doses or vehicle were substituted for cocaine for a period of 15 or more days each, with re-establishment of responding under cocaine after each substitution. Evaluation of a wide range of methocarbamol doses (1.0-32mg/kg/injection) showed that this compound maintained rates of self-injection at vehicle control levels, which were below those maintained by cocaine. The discriminative stimulus effects of methocarbamol were studied in baboons trained to discriminate either lorazepam (1.8mg/kg, p.o.) or pentobarbital (10.0mg/kg, p.o.) from the no-drug condition and in rats trained to discriminate lorazepam (1.0mg/kg, i.p.), diazepam (1.0mg/kg, i.p.), or pentobarbital (10.0mg/kg, i.p.) from the no-drug condition using a two-lever, food-maintained drug discrimination procedure. Evaluation of a range of doses in baboons (10-180mg/kg, p.o.) and rats (32-180mg/kg, i.p.) showed that methocarbamol did not occasion drug-lever responding at any dose. Methocarbamol did not produce changes in response rates in baboons, but higher doses severely suppressed response rates in rats. The present experiments show that the behavioral profile of methocarbamol is clearly distinguishable from that of barbiturates and benzodiazepines. Taken together with analogous studies with other sedative-anxiolytic drugs, these results suggest that methocarbamol has a relatively low likelihood of abuse.

Journal Article↗

Methocarbamol degradation in aqueous solution.

The kinetics of the hydrolysis of methocarbamol to the corresponding diol guaifenesin in aqueous solution was studied. Methocarbamol was rather stable in acidic media but easily hydrolyzed in alkaline solution. The formation of an unknown compound, proved to be an isomer of methocarbamol [the 3-(2-methoxyphenoxy)-propanediol 2-carbamate] is involved. The amounts of methocarbamol and the two degradation products resulting from storage of methocarbamol in various buffer solutions over a pH range of 8.0 to 10.0 at 70-80 degrees C (ionic strength, 0.5 M), were followed as a function of time by a reversed-phase HPLC stability-indicating method to clarify the degradation pathway of methocarbamol in alkaline solutions. Analysis of the concentration-time profiles reveals that base-catalyzed methocarbamol hydrolysis proceeded mainly through the formation of its isomer. The observed degradation rates followed approximately pseudo-first-order kinetics at constant pH and temperature.

Drug Stability↗

High-performance liquid chromatographic analysis of methocarbamol enantiomers in biological fluids.

Methocarbamol enantiomers in rat and human plasma were quantified using a stereospecific high-performance liquid chromatographic method. Racemic methocarbamol and internal standard, (R)-(-)-flecainide, were isolated from plasma by a single-step extraction with ethyl acetate. After derivatization with the enantiomerically pure reagent (S)-(+)-1-(1-naphthyl)ethyl isocyanate, methocarbamol diastereomers and the (R)-flecainide derivative were separated on a normal-phase silica column with a mobile phase consisting of hexane-isopropanol (95:5, v/v) at a flow-rate of 1.6 ml/min. Ultraviolet detection was carried out at a wavelength of 280 nm. The resolution factor between the diastereomers was 2.1 (alpha = 1.24). An excellent linearity was observed between the methocarbamol diastereomers/internal standard derivative peak-area ratios and plasma concentrations, and the intra- and inter-day coefficients of variation were always < 9.8%. The lowest quantifiable concentration was 0.5 microgram/ml for each enantiomer (coefficients of variation of 9.8 and 8.8% for (S)- and (R)-methocarbamol, respectively), while the limit of detection (signal-to-noise ratio 3:1) was approximately 10 ng/ml. The assay was used to study the pharmacokinetics of methocarbamol enantiomers in a rat following intravenous administration of a 120 mg/kg dose of racemic methocarbamol and to evaluate plasma and urine concentrations in a human volunteer after oral administration of a 1000-mg dose of the racemate. The method is suitable for stereoselective pharmacokinetic studies in humans as well as in animal models.

Animals↗

Evaluation of the abuse potential of methocarbamol.

The subjective and behavioral effects of p.o. administered methocarbamol, lorazepam and placebo were studied in a nonresidential group of adult male volunteers with histories of recreational substance abuse including sedative/hypnotics. In the first phase of the investigation, a dose run-up of methocarbamol (up to 12 g) was conducted in six subjects to determine appropriate doses. In the second phase, a randomized block cross-over study using 14 subjects was conducted. The following drug conditions were tested in the cross-over phase: placebo, lorazepam 1, 2 and 4 mg, and methocarbamol 2.25, 4.5 and 9 g. Drug conditions were tested under double-blind conditions. Psychomotor and cognitive performance measures and subject- and observer-rated behavioral responses were measured daily before dosing and for 5.5 hr after drug administration. The results showed that both lorazepam and methocarbamol produced statistically significant dose-related increases in subjects' ratings of drug effect and liking, although only lorazepam increased morphine-benzedrine group (MGB) scale scores. Methocarbamol also increased ratings on measures indicating the emergence of dysphoric and other side effects at high doses. Both drugs impaired psychomotor and cognitive performance, with lorazepam generally producing greater effects than methocarbamol. The results indicate that methocarbamol, at doses well above those used therapeutically, has some potential to be abused by persons with histories of sedative/hypnotic abuse; however, this potential for abuse is probably decreased by the accompanying side effects at high doses and is probably less than that of lorazepam.

Adolescent↗

The pharmacology and pharmacokinetics of high-dose methocarbamol in horses.

The haemodynamic, respiratory and behavioural effects and pharmacokinetics of methocarbamol were studied in eight healthy, adult horses after intravenous (i.v.) and oral administration of large dosages. Heart rate, cardiac output, mean pulmonary arterial blood pressure, systolic, diastolic and mean aortic blood pressure, respiratory rate and arterial blood gases did not change after either i.v. (30 mg/kg bodyweight [bwt]) or oral (50 and 100 mg/kg bwt) dosages of methocarbamol. Mild to moderate depression was observed in five of eight horses administered i.v. methocarbamol, and in all horses administered oral methocarbamol. Plasma methocarbamol concentration declined very rapidly during the initial or rapid disposition phase after i.v. administration; the terminal elimination half-life ranged from 59 to 90 mins. Peak plasma methocarbamol concentrations following oral administration occurred within 15 to 45 mins and oral bioavailability ranged from 50.7 to 124 percent.

Administration, Oral↗

Muscle relaxant activity of methocarbamol enantiomers in mice.

Documented studies support the emerging idea that drug enantiomers could have different pharmacological activity. Our bibliographical data have shown that so far no report has been published on the pharmacological activity of individual enantiomers of methocarbamol. This study was conducted to characterize the muscle relaxant activity of methocarbamol enantiomers. The rotarod test was used to compare the muscle relaxant activity of racemic methocarbamol and pure enantiomers after intraperitoneal administration of the enantiomers to mice. The results show that (+)-R-methocarbamol has higher muscle relaxant activity compared with racemic methocarbamol or (-)-S-methocarbamol.

Animals↗

A fatal interaction of methocarbamol and ethanol in an accidental poisoning.

A case is presented of a fatal drug interaction caused by ingestion of methocarbamol (Robaxin) and ethanol. Methocarbamol is a carbamate derivative used as a muscle relaxant with sedative effects. Therapeutic concentrations of methocarbamol are reported to be 24 to 41 micrograms/mL. Biological fluids were screened for ethanol using the Abbott TDx system and quantitated by gas-liquid chromatography (GLC). Determination of methocarbamol concentrations in biological tissue homogenates and fluids were obtained by colorimetric analysis of diazotized methocarbamol. Blood ethanol concentration was 135 mg/dL (0.135% w/v) and urine ethanol was 249 mg/dL (0.249% w/v). Methocarbamol concentrations were: blood, 257 micrograms/mL; bile, 927 micrograms/L; urine, 255 micrograms/L; gastric, 3.7 g; liver, 459 micrograms/g; and kidney, 83 micrograms/g. The combination of ethanol and carbamates is contraindicated since acute alcohol intoxication combined with carbamate usage can lead to combined central nervous system depression as a result of the interactive sedative-hypnotic properties of the compounds.

Adult↗

Hemolytic potential of methocarbamol.

Methocarbamol, a compound related to mephenesin, has in vitro hemolytic potential. A study was performed to determine whether any hemolysis was detectable after intravenous injection. Methocarbamol and its vehicle (50% polyethylene glycol-300) was compared with vehicle alone and with normal saline controls in high- and low-dose regimens in normal volunteers. Significant increases in plasma hemoglobin were detected 30 min after intravenous injection of methocarbamol or its vehicle alone. Maximum initial plasma hemoglobin levels were approximately 10 mg/dl with vehicle alone, but only 4 mg/dl with the methocarbamol added. Serum haptoglobin levels fell after both high-dose methocarbamol and vehicle during the 3-day period of treatment. Hemolysis, though detectable, did not exceed levels found under physiologic circumstances such as exercise, and represents only a small fraction of the normal daily hemolysis of aged erythrocytes.

Adult↗

Metabolism of methocarbamol (robaxin) in the isolated perfused rat liver and identification of glucuronides.

1. Permethylation and g.l.c.-mass spectrometric analysis of bile from an isolated rat liver perfusion to which methocarmol was added showed seven components not present in control bile: methocarbamol, glucuronides of methocarbamol and desmethyl-methocarbamol, and four glucuronides of hydroxylated methocarbamol metabolites. 2. An interesting rearrangement of a methyl group has been found in the mass spectrum of 3-(2-methoxyphenyloxy)-1,2-dimethoxypropane, the permethylation product from methocarbamol.

Animals↗

Pharmacologic and pharmacokinetic properties of methocarbamol in the horse.

The hemodynamic, respiratory, and behavioral effects, as well as the pharmacokinetic properties of methocarbamol, were determined in horses. Heart rate, cardiac output, arterial and venous blood pressures, respiratory rate, and arterial blood gases did not change after IV methocarbamol (4.4, 8.8, 17.6 mg/kg) administration. There were no signs of behavior modification or ataxia observed. Analysis of plasma concentration time data indicated that the disposition of methocarbamol may be dose-dependent. Clearance and steady-state volume of distribution decreased as the dose increased. Plasma concentrations of guaifenesin, a metabolite of methocarbamol, were never greater than 0.5% of the plasma concentration of methocarbamol.

Animals↗

Pharmacokinetics and protein binding of methocarbamol in renal insufficiency and normals.

We determined plasma methocarbamol concentrations over 24 h following a 1.5 g methocarbamol dose (off-dialysis day) to 8 chronic haemodialysis patients and compared these results to those from 17 healthy male volunteers. The harmonic mean elimination half-life was similar between the two groups, 1.24 and 1.14 h, respectively. tmax and the weight-adjusted Cmax were 1.1 h and 27.0 mg.m-1 for haemodialysis patients and 1.1 and 23.1 mg.l-1 for normals. Relative systemic availability was assessed by comparing weight-normalized AUC x k10 products. These results indicate no significant differences with respect to methocarbamol absorption, with the relative systemic availability in patients being 113%. These data suggest that absorption and elimination of methocarbamol is similar between normal subjects and patients undergoing maintenance haemodialysis.

Chromatography, High Pressure Liquid↗

Subjective and behavioral effects of diphenhydramine, lorazepam and methocarbamol: evaluation of abuse liability.

The effects of orally administered placebo, diphenhydramine, lorazepam, methocarbamol and placebo were studied in volunteers with histories of recreational substance abuse including sedative/hypnotics. Placebo, diphenhydramine (100, 200 and 400 mg), lorazepam (1 and 4 mg) and methocarbamol (2.25 and 9 g) were tested in a randomized, double-blind crossover study using 14 subjects. Psychomotor and cognitive performance and subject- and observer-rated responses were measured daily before and for 5.5 hr after drug administration. The results showed that each of the drugs exhibited a different profile of effects on the test battery. Lorazepam produced significant increases in subjects' ratings of drug effect and liking, increases in measures of sedation and impairment of psychomotor performance. Methocarbamol also produced significant increases in subjects' ratings of drug effect and liking and measures of sedation, but it produced only minor impairment of psychomotor and cognitive performance. Diphenhydramine increased subjects' and observers' ratings of drug effect and measures of sedation, but it produced less psychomotor performance impairment and liking than lorazepam. Diphenhydramine produced the most side effects. The present study clearly differentiated the behavioral and subjective profiles of diphenhydramine, lorazepam and methocarbamol. Consistent with its recognized low abuse liability, diphenhydramine produced fewer increases in measures of positive mood and more adverse effects. The considerable overlap in subjective effect measures of positive mood make further differentiation with respect to abuse liability difficult.

Adult↗

Development and validation of a high-performance liquid chromatographic method for the determination of methocarbamol in human plasma.

An isocratic HPLC method was developed and validated for the quantitation of methocarbamol in human plasma. Methocarbamol and internal standard in 200 microliters of human plasma were extracted with ethyl acetate, evaporated to dryness and reconstituted in water. Separation was achieved on a reversed-phase C18 column with a mobile phase of methanol-0.1 M potassium phosphate monobasic-water (35:10:55, v/v/v). The detection was by ultraviolet at 272 nm. Linearity was established at 1-100 micrograms/ml (r > 0.999). The limit of quantitation was designed as 1 microgram/ml to suit pharmacokinetic studies. Inter-day precision and accuracy of the calibration standards were 1.0 to 3.6% coefficients of variance (C.V.) and -2.0 to +1.6% relative error (R.E.). Quality controls of 3, 20 and 70 micrograms/ml showed inter-day precision and accuracy of 2.5 to 3.6% C.V. and -0.9 to -0.4% R.E. Recovery of methocarbamol was 91.4-100.3% in five different lots of plasma. The method was shown to be applicable on different brands of C18 columns.

Chromatography, High Pressure Liquid↗

Some studies on peripheral actions of mephenesin, methocarbamol and diazepam.

1. Mephenesin, methocarbamol and diazepam abolished polysynaptic reflex contractions of the cat tibialis anterior muscle elicited by stimulation of the homolateral femoral nerve.2. Mephenesin and methocarbamol caused a prolongation of the mean refractory period of directly or indirectly stimulated skeletal muscle. These effects were due to a direct action on the muscle fibres. There was no effect on responses to single stimuli.3. The increase in refractory period produced by mephenesin was greater in indirectly than in directly stimulated rat diaphragms. Experiments using the isolated phrenic nerve suggest that this difference is due to the local anaesthetic action of mephenesin.4. In the indirectly stimulated cat tibialis anterior muscle high frequency stimulation resulted in a non-maintained tetanus in the presence of mephenesin and methocarbamol.5. Diazepam was without peripheral effects on the responses of skeletal muscle.6. The results with mephenesin and methocarbamol are discussed in relation to their mode of action in reducing muscle spasm.

Action Potentials↗

Mephenesin, methocarbamol, chlordiazepoxide and diazepam: actions on spinal reflexes and ventral root potentials.

1. Dose levels of mephenesin, methocarbamol, chlordiazepoxide and diazepam which abolished polysynaptic reflex contractions had no effect on monosynaptic knee-jerk reflexes in chloralose anaesthetized cats.2. Ventral root potentials were recorded following stimulation of the corresponding dorsal root (L7 or S1), and the areas of the mono- and polysynaptic components were measured by planimetry.3. Dose levels of the drugs which abolished polysynaptic reflex contractions reduced the areas of the polysynaptic component of the ventral root potentials by about 50%. Mephenesin and methocarbamol reduced the area of the monosynaptic component to a similar extent. Chlordiazepoxide was less potent in this respect while diazepam was without effect at this dose level.4. Linear regression lines were calculated for the reduction in the mono- and polysynaptic components of ventral root potentials with increasing doses of each of the four drugs. With methocarbamol and mephenesin the lines were parallel and coincident. With chlordiazepoxide and diazepam they were parallel but not coincident. Large doses of diazepam were required to reduce the area of the monosynaptic component, this drug being the only one of the four tested to have a differential action on the two components which was statistically significant.5. The results are discussed in terms of depressant actions of the drugs on alpha-motorneurones, effects of the drugs at higher centres concerned with motor function, and the lack of evidence that spinal interneurones represent a specific site of action for centrally acting skeletal muscle relaxants.

Animals↗

Does methocarbamol affect fatigue markers in the low-back electromyogram?

Many low-back patients undergo electromyography (EMG)-based evaluations of muscle performance but present to the clinic after being prescribed muscle relaxants. The question that needed to be addressed was, do centrally acting muscle relaxants (methocarbamol; Robaxin) affect the EMG spectral indices of muscle fatigue that are often used to assess muscle performance. Participants performed an isometric spine extension protocol involving a 30 s fatigue exertion trial, then 1 min rest, and finally a 10 s long repeat exertion trial, at a 60% maximum voluntary contraction (MVC) level of exertion. Seven men were tested on two separate days (approximately 3-7 days apart), one day while medicated (six doses) with Robaxin and on another while not medicated. Specifically, the following parameters were studied in the bilateral multifidus (L5), lower erector spinae (L3) and upper erector spinae (T9): the slope of median power frequencies (MPFs) over the duration of the trial and the initial y-intercept of the MPF. The results generally suggest that methocarbamol (Robaxin) does not have any significant affect on the EMG median power frequency of the extensors during a fatiguing contraction followed by a repeat exertion, at least in normal people (one exception was observed--one side of multifidus at L5). However, given that this appears to be the first study of its kind, and that a relatively small number of subjects were used in this study, further investigation is needed to make a definitive conclusion about the effects of this drug on the several features of the electromyogram, over a broad spectrum of the clinical population performing a wider variety of tasks.

Adult↗

Determination of methocarbamol in equine serum and urine by high-performance liquid chromatography with ultraviolet detection and atmospheric pressure ionization-mass spectrometric confirmation.

Urine and serum samples collected from four standard-bred mares after and oral regimen administration of methocarbamol were extracted and analyzed. The method consisted of enzyme hydrolysis followed by a one-step liquid-liquid extraction, separation on a reversed-phase (RP-18) column, and detection using an ultraviolet (UV) detector. The confirmation was carried out using a liquid chromatography-atmospheric pressure ionization-mass spectrometry (LC-API-MS) system. Maximum methocarbamol concentrations of 1498, 1734, 1547, 2322 micrograms/mL in urine and 4.9, 1.7, and 3.6 micrograms/mL in serum were observed. The peak concentrations of the drug were detected 1-4 h (urine) and 10-60 min (serum) after administration to four horses. The method validation results and drug elimination profiles for both urine and serum are presented and discussed.

Animals↗

A double-blind trial of methocarbamol versus placebo in painful muscle spasm.

A double-blind trial of methocarbamol versus placebo was carried out in 59 matched pairs of patients suffering from painful muscle spasm. Methocarbamol (1500 mg. q.d.s.) was found to be effective in approximately 60% of patients compared with 30% of patients receiving placebo (p less than 0.01). Side-effects were of almost equal incidence in the two groups.

Adult↗