Orphenadrine

Source: Wikipedia, the free encyclopedia.
Orphenadrine
Clinical data
Trade namesGeneric; many brand names[1]
AHFS/Drugs.comMonograph
MedlinePlusa682162
Pregnancy
category
  • AU: B2
Routes of
administration		Oral, intravenous, intramuscular
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: OTC
  • NZ: Prescription only
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability90%
Protein binding95%
MetabolismHepatic demethylation
Elimination half-life13–20 hours[2]
ExcretionRenal and biliary
Identifiers
  • (RS)-N,N-Dimethyl-2-[(2-methylphenyl)-phenyl-methoxy]-ethanamine
JSmol)
  • O(CCN(C)C)C(c1ccccc1)c2ccccc2C
  • InChI=1S/C18H23NO/c1-15-9-7-8-12-17(15)18(20-14-13-19(2)3)16-10-5-4-6-11-16/h4-12,18H,13-14H2,1-3H3 checkY
  • Key:QVYRGXJJSLMXQH-UHFFFAOYSA-N checkY
  (verify)

Orphenadrine (sold under many

brand names)[1] is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs.[citation needed] It is considered a dirty drug due to its multiple mechanisms of action in different pathways.[citation needed
] It was discovered and developed in the 1940s.

Medical use

Orphenadrine is a skeletal muscle relaxant.

sprains, in combination with rest and physical therapy.[3] 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.[4]

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.[5]

In 2003, a

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cross-over study of orphenadrine vs placebo.[6] Although orphenadrine and other anticholinergics have largely been superseded by other drugs; they have a use in alleviating motor function symptoms, and appear to help about 20% of people with Parkinson's.[7]

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, constipation, urine retention, blurred vision, and headache.[3] Its use in Parkinson's is especially limited by these factors.[6]

Orphenadrine is contraindicated in patients with

bladder disorders; that is, they should not consume this drug.[8]

Continuous and/or cumulative use of anticholinergic medications, including first-generation antihistamines, is associated with higher risk of cognitive decline and dementia in older people.[9][10]

Pharmacology

Orphenadrine is known to have these pharmacological properties:

History

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.[21]

Prior to the development of amantadine in the late 1960s and then other drugs, anticholinergics like orphenadrine were the mainstay of Parkinson's treatment.[7]

Formulation

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][22]

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.[23]

Chemistry

Orphenadrine is a

phenyl rings.[24]

Stereochemistry

Orphenadrine has a

racemate.[25]

Enantiomers

(R)-orphenadrine
CAS number: 33425-91-1
(S)-orphenadrine
CAS number: 33425-89-7

References

  1. ^ a b c d e "Orphenadrine". Drugs.com international listings. Retrieved 5 February 2016.
  2. S2CID 24631265
    .
  3. ^ a b c "Orphenadrine". Medline Plus. 1 December 2010. Retrieved 6 February 2016.
  4. PMID 15276195
    .
  5. S2CID 205197256
    .
  6. ^
    PMID 12804486
    .
  7. ^
    ISBN 978-0-19-261911-2
    .
  8. ^ "Orphenadrine Citrate Extended release label" (PDF). U.S. Food and Drug Administration. October 1998. Archived (PDF) from the original on 2023-10-04. Retrieved 2023-10-04.
  9. PMID 25621434
    .
  10. PMID 19636034
    .
  11. PMID 3353357
    .
  12. ^ Nurses' Drug Guide 2010 [full citation needed]
  13. ^
    PMID 2578597
    .
  14. S2CID 10142765
    .
  15. S2CID 10142765
    .
  16. PMID 12232776
    .
  17. S2CID 31845784
    .
  18. PMID 26106364
    .
  19. S2CID 17830280
    .
  20. S2CID 20049051
    .
  21. ISBN 978-0-471-89979-2
    .
  22. ^ "FDA listing of Orphenadrine citrate registrations". United States Food and Drug Administration. Retrieved 6 February 2016.
  23. ^ "Disipal Brand of Orphenadrine HCl". Riker.
  24. ISBN 978-0-12-417213-5
    .
  25. ISBN 978-3-946057-10-9
    .

External links