Orphenadrine (sold under many brand names worldwide[1]) is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine (orphenadrine is chemically known as monomethyldiphenhydramine). It is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. This substance is considered a dirty drug due to its multiple mechanism of action in different pathways. It was discovered and developed in the 1940s.

Clinical data
Trade namesGeneric; many brand names worldwide[1]
  • AU: B2
  • US: C (Risk not ruled out)
    Routes of
    Oral, intravenous, intramuscular
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding95%
    MetabolismHepatic demethylation
    Elimination half-life13-20 hours[2]
    ExcretionRenal and biliary
    CAS Number
    PubChem CID
    CompTox Dashboard (EPA)
    ECHA InfoCard100.001.372
    Chemical and physical data
    Molar mass269.388 g·mol−1
    3D model (JSmol)

    As of 2015, the cost for a typical month of medication in the United States is US$25 to 50.[3]

    Medical use

    Orphenadrine is used to relieve pain caused by muscle injuries like strains and sprains in combination with rest and physical therapy.[4] A 2004 review found fair evidence that orphenadrine is effective for acute back or neck pain, but found insufficient evidence to establish the relative efficacy of the drug in relation to other drugs in the study.[5]

    Orphenadrine and other muscle relaxants are sometimes used to treat pain arising from rheumatoid arthritis but there is no evidence they are effective for that purpose.[6]

    A 2003 Cochrane Review of the use of anticholinergic drugs to improve motor function in Parkinson's disease found that as a class, the drugs are useful for that purpose; it identified one single-site randomised, cross-over study of orphenadrine vs placebo.[7] Orphenadrine and other anticholinergics have largely been superseded by other drugs; they have a use in alleviating motor function symptoms, and appear to help about 20% of people with Parkinson's.[8]

    Side effects

    Orphenadrine has the side effects of the other common antihistamines in large part. Stimulation is somewhat more common than with other related antihistamines, and is especially common in the elderly. Common side effects include dry mouth, dizziness, drowsiness, upset stomach or vomiting, constipation, urine retention, blurred vision, and headache.[4] Its use in Parkinson's is especially limited by these factors.[7]

    People with glaucoma, digestive problems such as peptic ulcers or bowel obstruction, or sphincter relaxation disorders, or with enlarged prostate, bladder problems, or myasthenia gravis, should not take this drug.[9]


    Orphenadrine is known to have this pharmacology:


    George Rieveschl was a professor of chemistry at the University of Cincinnati and led a research program working on antihistamines. In 1943, one of his students, Fred Huber, synthesized diphenhydramine. Rieveschl worked with Parke-Davis to test the compound, and the company licensed the patent from him. In 1947 Parke-Davis hired him as their Director of Research. While he was there, he led the development of orphenadrine, an analog of diphenhydramine.[19]

    Prior to the development of amantadine in the late 1960s and then other drugs, anticholinergics like orphenadrine were the mainstay of Parkinson's treatment.[8]


    Orphenadrine has been available as a citrate salt and a hydrochloride salt; in the US as of February 2016 the citrate form was available in tablets, extended release tablets, compounding powder and by injection for acute use in a hospital setting.[1][20]

    Orphenadrine is often available mixed with aspirin, paracetamol/acetaminophen, ibuprofen, caffeine, and/or codeine.[1]

    The brand names Norflex and Norgesic are formulations of the citrate salt of orphenadrine and Disipal is the hydrochloride salt.[21]


    Orphenadrine is a derivative of diphenhydramine with a methyl group added to one of the phenyl rings.[22]

    Tofenacin is the N-desmethyl analogue of orphenadrine and an antidepressant.


    Orphenadrine has a chiral center and two enantiomers. Medictions are racemates.[23]


    CAS number: 33425-91-1

    CAS number: 33425-89-7


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    7. Katzenschlager R, Sampaio C, Costa J, Lees A (2003). "Anticholinergics for symptomatic management of Parkinson's disease". The Cochrane Database of Systematic Reviews (2): CD003735. doi:10.1002/14651858.CD003735. PMID 12804486.
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    11. Nurses' Drug Guide 2010
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    18. Scholz EP, Konrad FM, Weiss DL, Zitron E, Kiesecker C, Bloehs R, et al. (December 2007). "Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656". Naunyn-Schmiedeberg's Archives of Pharmacology. 376 (4): 275–84. doi:10.1007/s00210-007-0202-6. PMID 17965852.
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