Orphenadrine (sold under many brand names worldwide) is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs.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.
|Trade names||Generic; many brand names worldwide|
|Oral, intravenous, intramuscular|
|Elimination half-life||13-20 hours|
|Excretion||Renal and biliary|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||269.388 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.
Orphenadrine is used to relieve pain caused by muscle injuries like strains and sprains in combination with rest and physical therapy. 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.
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. Orphenadrine and other anticholinergics have largely been superseded by other drugs; they have a use in alleviating motor function symptoms, and appear to help about 20% of people with Parkinson's.
Orphenadrine is an example of an anticholinergic which has analgesia of its own; doctors and scientists have known this since the late 1940s and developed about the same were amitriptyline and cyclobenzaprine, which are used for neuropathic pain and pain accompanied by muscle spasm. Like the other two, orphenadrine can be used by oral, injected, and topical routes of administration.
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. Its use in Parkinson's is especially limited by these factors.
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.
Orphenadrine is known to have this pharmacology:
- Nonselective mACh receptor antagonist (anticholinergic, 58% as potent as atropine) Various monographs and package inserts, nursing manuals, journal articles and so forth have proposed the theory that this anticholinergic (atropine-like) activity, NMDA antagonism and possible local anaesthetic and miscellaneous analgesic effects may be the reason for orphenadrine's efficacy against muscle and other pain. These reasons are behind the use of orphenadrine and other drugs of a number of types which are used with paracetamol, aspirin, naproxen, and similar agents with or without opioid analgesics to more effectively manage pain of various types.
- H1 receptor antagonist (antihistamine)
- NMDA receptor antagonist (Ki-value of 6.0 +/- 0.7 μM, one third as potent as phencyclidine, which binds with a Ki of 2 μM)
- NET blocker (norepinephrine reuptake inhibitor)
- Nav1.7, Nav1.8, and Nav1.9 sodium channel blocker
- HERG potassium channel blocker
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.
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.
The brand names Norflex and Norgesic are formulations of the citrate salt of orphenadrine and Disipal is the main hydrochloride salt
CAS number: 33425-91-1
CAS number: 33425-89-7
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