orphenadrine hydrochloride

Trade name: disipal

Small moleculeapproved

Approved

May 10, 1957

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs. Orphenadrine binds and inhibits both histamine H1 receptors and NMDA receptors. It restores the motor disturbances induced by neuroleptics, in particular, the hyperkinesia. The dopamine deficiency in the striatum increases the stimulating effects of the cholinergic system. This stimulation is counteracted by the anticholinergic effect of orphenadrine. It may have a relaxing effect on skeletal muscle spasms and it has a mood elevating effect. Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favorable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. Adverse reactions of orphenadrine citrate are mainly due to the mild anticholinergic action of orphenadrine citrate and are usually associated with higher dosage. Dryness of the mouth is usually the first adverse effect to appear. When the daily dose is increased, possible adverse effects include tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilatation of pupils, increased ocular tension, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness, hypersensitivity reactions, pruritus, hallucinations, agitation, tremor, gastric irritation and rarely urticaria and other dermatoses — NCATS

Clinical trial activity

11 trials · 18 clinical orgs · 23 marketing orgs

Phase 1
1
Phase 2
2
Phase 3
2
Phase 4
6

Earliest trial started Dec 1, 2010 (NCT01263652)

Timeline

1950s

  1. May 10, 1957

    3M — Earliest FDA Approval

  2. May 10, 1957

    3M — NDA Secondary Org

  3. May 10, 1957

    3M — NDA Organization

  4. Nov 4, 1959

    Medicis — NDA Secondary Org

  5. Nov 4, 1959

    Bausch Health Companies — NDA Secondary Org

1960s

  1. Oct 2, 1960

    Teligent Pharmaceuticals — NDA Secondary Org

  2. Oct 2, 1960

    Pharmaceutical Associates — Marketing Organization

  3. Oct 2, 1960

    Pharmaceutical Associates — NDA Secondary Org

1980s

  1. Jul 16, 1981

    Watson Pharmaceuticals — Marketing Organization

  2. Jun 29, 1982

    Sandoz — Marketing Organization

1990s

  1. Nov 27, 1996

    Novartis — Marketing Organization

  2. Nov 27, 1996

    Chartwell Pharmaceuticals — Marketing Organization

  3. May 29, 1998

    Galt Pharmaceuticals — Marketing Organization

  4. Jun 19, 1998

    Lupin — Marketing Organization

  5. Jan 29, 1999

    ANDA Repository — Marketing Organization

  6. Jan 29, 1999

    Rising Pharmaceuticals — Marketing Organization

  7. Apr 30, 1999

    Jerome Stevens Pharmaceuticals — Marketing Organization

2000s

  1. Jun 23, 2000

    Impax Laboratories — Marketing Organization

  2. Mar 4, 2003

    West-Ward Pharmaceutical — Marketing Organization

  3. Mar 4, 2003

    Hikma — Marketing Organization

  4. May 24, 2006

    Akorn, Inc. — Marketing Organization

2010s

  1. Aug 30, 2011

    Sagent Pharmaceuticals, Inc. — Marketing Organization

  2. Jul 27, 2012

    Invagen Pharms — Marketing Organization

  3. Jul 27, 2012

    Bayshore Pharms Llc — Marketing Organization

  4. Jul 27, 2012

    Unichem — Marketing Organization

  5. Jan 1, 2015

    Earliest Phase 1 Sponsor(trial)

  6. Jan 1, 2015

    Earliest Phase 3 Sponsor(trial)

Indications

Mechanism of action

Combination products

Approval history

  • approvedMay 10, 1957

Chemistry & pharmacology

Loading structure…

SMILES

CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2C
Mol. weight
269.3813 g/mol
Lipinski Ro5
Pass
Rule of 3
No
Chirality
Racemic Mixture
Inorganic
No
Polymer
No
Delivery
Oral, Parenteral
Availability
Prescription Only

Oral

Yes

Parenteral

Yes

Topical

No

Sources

Also known as

  • 2-methyldiphenhydramine
  • 2-methyldiphenhydramine
  • 2-(phenyl-o-tolylmethoxy)ethyldimethylamine
  • 2-(phenyl-o-tolylmethoxy)ethyldimethylamine
  • beta-dimethylaminoethyl 2-methylbenzhydryl ether
  • beta-dimethylaminoethyl 2-methylbenzhydryl ether
  • biorphen
  • biorphen
  • dimethyl-[2-(phenyl-o-tolyl-methoxy)-ethyl]-amine
  • dimethyl-[2-(phenyl-o-tolyl-methoxy)-ethyl]-amine
  • disipal
  • disipal
  • disipal
  • disipal
  • disipal
  • disipal
  • disipal
  • invagesic
  • invagesic
  • n,n-dimethyl-2-(alpha-2-tolylbenzoyloxy)ethylamine
  • n,n-dimethyl-2-(alpha-2-tolylbenzoyloxy)ethylamine
  • n,n-dimethyl-2-[(o-methyl-alpha-phenylbenzyl)oxy]ethylamine
  • n,n-dimethyl-2-[(o-methyl-alpha-phenylbenzyl)oxy]ethylamine
  • n,n-dimethyl-2-(phenyl(o-tolyl)methoxy)ethanamine
  • n,n-dimethyl-2-(phenyl(o-tolyl)methoxy)ethanamine
  • norflex
  • norflex
  • norgesic
  • norgesic
  • o-methyldiphenhydramine
  • o-methyldiphenhydramine
  • o-monomethyldiphenhydramine
  • o-monomethyldiphenhydramine
  • orfenadrina
  • orfenadrina
  • orphenadine
  • orphenadine citrate
  • orphenadine citrate
  • orphenadrin
  • orphenadrine
  • orphenadrine
  • orphenadrine
  • orphenadrine
  • orphenadrine
  • orphenadrine
  • orphenadrine
  • orphenadrine
  • orphenadrine caffeine
  • orphenadrine chloride
  • orphenadrine chloride
  • orphenadrine (chloride)
  • orphenadrine (chloride)
  • orphenadrine (chloride)
  • orphenadrine citrate
  • orphenadrine citrate
  • orphenadrine citrate
  • orphenadrine citrate
  • orphenadrine (citrate)
  • orphenadrine (citrate)
  • orphenadrine hcl
  • orphenadrine hcl
  • orphenadrine hcl
  • orphenadrine hydrochloride
  • orphenadrine hydrochloride
  • orphenadrinum
  • orphenadrinum
  • orphengesic
  • phenyl-o-tolylmethyl dimethyaminoethyl ether
  • phenyl-o-tolylmethyl dimethyaminoethyl ether
  • β-dimethylaminoethyl 2-methylbenzhydryl ether
  • β-dimethylaminoethyl 2-methylbenzhydryl ether

Clinical trials

NCT IDPhaseStart dateSponsor(s)
NCT05413902Phase 4Apr 5, 2021University of Puerto Rico
NCT04509336N/AMay 20, 2020Mansoura University, Tanta University
NCT04835116Phase 4Apr 11, 2019Government of India, Government of Pakistan
NCT03493490Phase 4Mar 1, 2018Medical University of Vienna
NCT02985671Phase 3Jun 1, 2017Ache Laboratorios Farmaceuticos S.A., Allergisa Pesquisa Dermato-Cosmetica LTDA, Association of Assistance to the Disabled Child, Center for the Development of Clinical Studies Brazil, Instituto Nacional de Traumatologia e Ortopedia
NCT02958566Phase 4Jan 1, 2017OSF HealthCare, University of Illinois
NCT02665286Phase 4Mar 1, 2016Yeshiva University
NCT02485145Early Phase 1 (Phase 1)Jul 1, 2015Transdermal Therapeutics, Inc., Yeshiva University
NCT02449369Phase 4Apr 1, 2015Advent Health, Sagent Pharmaceuticals, Inc.
NCT02423395Phase 3Jan 1, 2015Tanta University
NCT01263652N/ADec 1, 2010Western Galilee Hospital
Showing 11 of 11 trials
Page 1 / 1

Organizations

Research & Development (18)

OrganizationOrg typeTrialsAs lead sponsorPhasesEarliest year
Tanta UniversityAcademic/Hospital2122015
Yeshiva UniversityAcademic/Hospital2122015
Ache Laboratorios Farmaceuticos S.A.For profit1112017
Advent HealthAcademic/Hospital1112015
Allergisa Pesquisa Dermato-Cosmetica LTDAFor profit1012017
Association of Assistance to the Disabled ChildAcademic/Hospital1012017
Center for the Development of Clinical Studies BrazilGovernment1012017
Government of IndiaGovernment1012019
Government of PakistanGovernment1112019
Instituto Nacional de Traumatologia e OrtopediaAcademic/Hospital1012017
Mansoura UniversityAcademic/Hospital1112020
Medical University of ViennaAcademic/Hospital1112018
OSF HealthCareAcademic/Hospital1012017
Sagent Pharmaceuticals, Inc.For profit1012015
Transdermal Therapeutics, Inc.For profit1112015
University of IllinoisAcademic/Hospital1112017
University of Puerto RicoAcademic/Hospital1112021
Western Galilee HospitalAcademic/Hospital1112010
18 organizations
Page 1 / 1

Marketing (25)

OrganizationOrg typeRelationshipDate
3MFor profitNDA2May 10, 1957
3MFor profitNDAMay 10, 1957
ANDA RepositoryFor profitMKTGJan 29, 1999
Akorn, Inc.For profitMKTGMay 24, 2006
Ascot PharmaceuticalsFor profitMKTG
Bausch Health CompaniesFor profitNDA2Nov 4, 1959
Bayshore Pharms LlcFor profitMKTGJul 27, 2012
Chartwell PharmaceuticalsFor profitMKTGNov 27, 1996
Galt PharmaceuticalsFor profitMKTGMay 29, 1998
HikmaFor profitMKTGMar 4, 2003
Impax LaboratoriesFor profitMKTGJun 23, 2000
Invagen PharmsFor profitMKTGJul 27, 2012
Jerome Stevens PharmaceuticalsFor profitMKTGApr 30, 1999
LupinFor profitMKTGJun 19, 1998
MedicisFor profitNDA2Nov 4, 1959
NovartisFor profitMKTGNov 27, 1996
Pharmaceutical AssociatesFor profitMKTGOct 2, 1960
Pharmaceutical AssociatesFor profitNDA2Oct 2, 1960
Rising PharmaceuticalsFor profitMKTGJan 29, 1999
Sagent Pharmaceuticals, Inc.For profitMKTGAug 30, 2011
SandozFor profitMKTGJun 29, 1982
Teligent PharmaceuticalsFor profitNDA2Oct 2, 1960
UnichemFor profitMKTGJul 27, 2012
Watson PharmaceuticalsFor profitMKTGJul 16, 1981
West-Ward PharmaceuticalFor profitMKTGMar 4, 2003