Orphenadrine

Overview

Orphenadrine 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relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s. WP⚠ Wikipedia itself has flagged this text: citation needed.

Uses, dosage and effects

Medical uses

Orphenadrine is a skeletal muscle relaxant. It is used to relieve pain caused by muscle injuries such as 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.[1][2][3] WP

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.[4] WP

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. Although orphenadrine and other anticholinergics have largely been superseded by other drugs; they have a use in alleviating motor function symptoms, and appear to help about 20% of people with Parkinson's.[5][6] WP

Risks and side effects

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. Its use in Parkinson's is especially limited by these factors.[2][5] WP

Orphenadrine is contraindicated in patients with glaucoma, myasthenia gravis, sphincter relaxation disorders, digestive problems such as peptic ulcers, bowel obstruction, or with enlarged prostate, bladder disorders; that is, they should not consume this drug.[7] WP

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.[8][9] WP

Pharmacology

Pharmacology

Orphenadrine is known to have these pharmacological properties: WP

• 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.[10][11][12] WP
• H₁ receptor antagonist (antihistamine)[12] WP
• NMDA receptor antagonist (Kᵢ value of 6.0 ± 0.7 μM, one hundred times less potent than phencyclidine, which binds with a Kᵢ of 59 nM)[13][14] WP
• NDRI (norepinephrine and dopamine reuptake inhibitor)[15][16] WP
• Naᵥ1.7, Naᵥ1.8, and Naᵥ1.9 sodium channel blocker[17] WP
• HERG potassium channel blocker[18] WP

History

History

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] WP

Prior to the development of amantadine in the late 1960s and then other drugs, anticholinergics like orphenadrine were the mainstay of Parkinson's treatment.[6] WP

Chemistry

Formula

C18H23NO PC

CAS number

83-98-7 PC

Molar mass (g/mol)

269.4 PC

IUPAC name (computed by PubChem)

N,N-dimethyl-2-[(2-methylphenyl)-phenylmethoxy]ethanamine PC

SMILES

CC1=CC=CC=C1C(C2=CC=CC=C2)OCCN(C)C PC

InChIKey

QVYRGXJJSLMXQH-UHFFFAOYSA-N PC

PubChem CID

4601

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Orphenadrine
2. Journal / agency Orphenadrine. 1 December 2010
3. Journal / agency Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. Journal of Pain and Symptom Management. August 2004. doi:10.1016/j.jpainsymman.2004.05.002 · PMID 15276195
4. Journal / agency Richards BL, Whittle SL, Buchbinder R. Muscle relaxants for pain management in rheumatoid arthritis. The Cochrane Database of Systematic Reviews. January 2012. doi:10.1002/14651858.CD008922.pub2 · PMID 22258993 · PMC11702505
5. Journal / agency Katzenschlager R, Sampaio C, Costa J, Lees A. Anticholinergics for symptomatic management of Parkinson's disease. The Cochrane Database of Systematic Reviews. 2003. doi:10.1002/14651858.CD003735 · PMID 12804486 · PMC8728160
6. Other Donaldson I, Marsden CD, Schneider S. Marsden's Book of Movement Disorders. 2012
7. Journal / agency Orphenadrine Citrate Extended release label. October 1998
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9. Journal / agency Carrière I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, Ancelin ML. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Archives of Internal Medicine. July 2009. doi:10.1001/archinternmed.2009.229 · PMID 19636034 · PMC2933398
10. Journal / agency Syvälahti EK, Kunelius R, Laurén L. Effects of antiparkinsonian drugs on muscarinic receptor binding in rat brain, heart and lung. Pharmacology & Toxicology. February 1988. doi:10.1111/j.1600-0773.1988.tb01852.x · PMID 3353357
11. Other Nurses' Drug Guide 2010 full
12. Journal / agency Rumore MM, Schlichting DA. Analgesic effects of antihistaminics. Life Sciences. February 1985. doi:10.1016/0024-3205(85)90252-8 · PMID 2578597
13. Journal / agency Kornhuber J, Parsons CG, Hartmann S, Retz W, Kamolz S, Thome J, Riederer P. Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies. Journal of Neural Transmission. General Section. 1995. doi:10.1007/BF01281158 · PMID 8788072
14. Journal / agency Kapur S, Seeman P. NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia. Molecular Psychiatry. 2002. doi:10.1038/sj.mp.4001093 · PMID 12232776
15. Journal / agency Pubill D, Canudas AM, Pallàs M, Sureda FX, Escubedo E, Camins A, Camarasa J. Assessment of the adrenergic effects of orphenadrine in rat vas deferens. The Journal of Pharmacy and Pharmacology. March 1999. doi:10.1211/0022357991772303 · PMID 10344632
16. Journal / agency Cheng MH, Block E, Hu F, Cobanoglu MC, Sorkin A, Bahar I. Insights into the Modulation of Dopamine Transporter Function by Amphetamine, Orphenadrine, and Cocaine Binding. Frontiers in Neurology. 2015. doi:10.3389/fneur.2015.00134 · PMID 26106364 · PMC4460958
17. Journal / agency Desaphy JF, Dipalma A, De Bellis M, Costanza T, Gaudioso C, Delmas P, George AL, Camerino DC. Involvement of voltage-gated sodium channels blockade in the analgesic effects of orphenadrine. Pain. April 2009. doi:10.1016/j.pain.2009.01.010 · PMID 19217209
18. Journal / agency Scholz EP, Konrad FM, Weiss DL, Zitron E, Kiesecker C, Bloehs R, Kulzer M, Thomas D, Kathöfer S, Bauer A, Maurer MH, Seemann G, Katus HA, Karle CA. Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656. Naunyn-Schmiedeberg's Archives of Pharmacology. December 2007. doi:10.1007/s00210-007-0202-6 · PMID 17965852
19. Other Sneader W. Drug Discovery: A History. 2005

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