Methocarbamol

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Methocarbamol
Methocarbamol2DCSD.svg
Systematic (IUPAC) name
(RS)-2-hydroxy-3-(2-methoxyphenoxy)propyl carbamate
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682579
Pregnancy cat.
Legal status
Routes Oral, intravenous
Pharmacokinetic data
Metabolism Hepatic
Half-life 1.14–1.24 hours[1]
Identifiers
CAS number 532-03-6 YesY
ATC code M03BA03
PubChem CID 4107
DrugBank DB00423
ChemSpider 3964 YesY
UNII 125OD7737X YesY
KEGG D00402 YesY
ChEBI CHEBI:6832 N
ChEMBL CHEMBL1201117 N
Chemical data
Formula C11H15NO5 
Mol. mass 241.241 g/mol
 N (what is this?)  (verify)

Methocarbamol is a central muscle relaxant used to treat skeletal muscle spasms. Under the trade name Robaxin, it is marketed by Actient Pharmaceuticals in the United States and Pfizer in Canada. The mechanism of action of methocarbamol is currently unknown, but may involve the inhibition of carbonic anhydrase.[2] The muscle relaxant effects of methocarbamol are largely attributed to central depressant effects;[3] however, peripheral effects of methocarbamol to prolong muscle refractory period have also been reported.[4]

Metabolism[edit]

Methocarbamol is the carbamate of guaifenesin, but does not produce guaifenesin as a metabolite, because the carbamate bond is not hydrolyzed metabolically; metabolism is by Phase I ring hydroxylation and O-demethylation, followed by Phase II conjugation. All the major metabolites are unhydrolyzed carbamates.[5][6]

Marketing[edit]

Generic Methocarbamol 750mg Oral Tablet.

Methocarbamol is marketed under different names when presented in combination with other active ingredients. In combination with acetaminophen (Paracetamol), under trade names Robaxacet and Tylenol Body Pain Night, whereas Robax Platinum is the trade name for a formulation of methocarbamol and ibuprofen.[7][8] A combination of methocarbamol and aspirin is marketed as Robaxisal, however in Spain the tradename Robaxisal is used for the Paracetamol combination instead of Robaxacet.

Abuse potential[edit]

Unlike other carbamates such as meprobamate and its prodrug carisoprodol, methocarbamol has greatly reduced abuse potential. Studies comparing it to lorazepam (Ativan) and diphenhydramine (Benadryl), along with placebo, find that methocarbamol produces increased "liking" responses and some sedative-like effects, however, at higher doses dysphoria is reported. It is considered to have an abuse profile similar to, but weaker than, lorazepam.[9]

Side-effects[edit]

Potential side-effects include: drowsiness, dizziness, clumsiness (ataxia), upset stomach, flushing, blurred vision, and fever. Both tachycardia (fast heart rate) and bradycardia (slow heart rate) have been reported;[10][11] these can be serious. Other serious side-effects include the development of a severe skin rash or itching, fainting, jaundice, persistent nausea/vomiting, stomach/abdominal pain, mental/mood changes, trouble urinating, signs of infection. If taken in large amounts at once or more than directed or as prescribed, dysphoria or suicidal thoughts may occur.[12] In addition, methocarbamol may cause urine to turn black, blue, or green. However, this effect is harmless.[13]

Methocarbamol has a high therapeutic index, i.e. a wide range of safe & effective dosages. Consumer (OTC) doses are in the range 3-6 gm/day,[14] while clinical doses can be as high as 24 gm/day for severe conditions such as tetanus.[15]

Because of potential for side-effects, this drug is considered to be a high-risk medication for the elderly.[16]

Chemistry[edit]

Methocarbamol can be synthesized from guaifenesin by successive reaction with phosgene and then ammonia.[17][18]

Methocarbamol synthesis

References[edit]

  1. ^ Sica DA, Comstock TJ, Davis J, Manning L, Powell R, Melikian A, Wright G. (1990). "Pharmacokinetics and protein binding of methocarbamol in renal insufficiency and normals". European Journal of Clinical Pharmacology 39 (2): 193–4. doi:10.1007/BF00280060. PMID 2253675. 
  2. ^ Parr JS, Khalifah RG. (1992). "Inhibition of carbonic anhydrases I and II by N-unsubstituted carbamate esters". J Biol Chem 267 (35): 25044–25050. PMID 1460006. 
  3. ^ Truitt EB Jr., Little JM. (1958). "A pharmacologic comparison of methocarbamol (AHR-85), the monocarbamate of 3-(o-methoxyphenoxy)-1,2-propanediol with chemically related interneuronal depressant drugs". J Pharmacol Exp Ther 122 (2): 239–246. PMID 13514612. 
  4. ^ Crankshaw DP, Raper C. (1968). "Some studies on peripheral actions of mephenesin, methocarbamol and diazepam". Br J Pharmacol 34 (3): 579–590. doi:10.1111/j.1476-5381.1968.tb08486.x. PMID 5726787. 
  5. ^ Methocarbamol. In: DRUGDEX System [intranet database]. Greenwood Village, Colorado: Thomson Healthcare; c1974–2009 [cited 2009 Feb 10].
  6. ^ Bruce RB, Turnbull LB, Newman JH. (Jan 1971). "Metabolism of methocarbamol in the rat, dog, and human". J Pharm Sci 60 (1): 104–106. doi:10.1002/jps.2600600120. PMID 5548215. 
  7. ^ "New Drugs and Indications Reviewed at the May 2003 DEC Meeting" (PDF). ESI Canada. Retrieved 2008-11-14. 
  8. ^ "Tylenol Body Pain Night Overview and Dosage" (website). Tylenol Canada. Retrieved 2012-04-23. 
  9. ^ "Subjective and behavioral effects of diphenhydramine, lorazepam and methocarbamol: evaluation of abuse liability". Journal of Pharmacology and Experimental Therapeutics. Retrieved 2011-05-06. 
  10. ^ medical-dictionary_thefreedictionary-methocarbamol
  11. ^ Drugs.com-methocarbamol-side-effects
  12. ^ METHOCARBAMOL – ORAL (Robaxin) side effects, medical uses, and drug interactions. Medicinenet.com. Retrieved on 2011-11-09.
  13. ^ Methocarbamol: MedlinePlus Drug Information. Nlm.nih.gov. Retrieved on 2011-11-09.
  14. ^ http://www.rxlist.com/robaxin-drug/indications-dosage.htm
  15. ^ http://www.drugs.com/dosage/methocarbamol.html
  16. ^ See NCQA’s HEDIS Measure: Use of High Risk Medications in the Elderly
  17. ^ R.S. Murphey, U.S. Patent 2,770,649 (1956)
  18. ^ Yale, H. L.; Pribyl, E. J.; Braker, W.; Bergeim, F. H.; Lott, W. A. (1950). Journal of the American Chemical Society 72 (8): 3710. doi:10.1021/ja01164a107.  edit