orphenadrine hydrochloride
Trade name: disipal
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class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs.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
Earliest trial started Dec 1, 2010 (NCT01263652)
Timeline
1950s
- May 10, 1957
3M — Earliest FDA Approval
- May 10, 1957
3M — NDA Secondary Org
- May 10, 1957
3M — NDA Organization
- Nov 4, 1959
Medicis — NDA Secondary Org
- Nov 4, 1959
Bausch Health Companies — NDA Secondary Org
1960s
- Oct 2, 1960
Teligent Pharmaceuticals — NDA Secondary Org
- Oct 2, 1960
Pharmaceutical Associates — Marketing Organization
- Oct 2, 1960
Pharmaceutical Associates — NDA Secondary Org
1980s
- Jul 16, 1981
Watson Pharmaceuticals — Marketing Organization
- Jun 29, 1982
Sandoz — Marketing Organization
1990s
- Nov 27, 1996
Novartis — Marketing Organization
- Nov 27, 1996
Chartwell Pharmaceuticals — Marketing Organization
- May 29, 1998
Galt Pharmaceuticals — Marketing Organization
- Jun 19, 1998
Lupin — Marketing Organization
- Jan 29, 1999
ANDA Repository — Marketing Organization
- Jan 29, 1999
Rising Pharmaceuticals — Marketing Organization
- Apr 30, 1999
Jerome Stevens Pharmaceuticals — Marketing Organization
2000s
- Jun 23, 2000
Impax Laboratories — Marketing Organization
- Mar 4, 2003
West-Ward Pharmaceutical — Marketing Organization
- Mar 4, 2003
Hikma — Marketing Organization
- May 24, 2006
Akorn, Inc. — Marketing Organization
2010s
- Aug 30, 2011
Sagent Pharmaceuticals, Inc. — Marketing Organization
- Jul 27, 2012
Invagen Pharms — Marketing Organization
- Jul 27, 2012
Bayshore Pharms Llc — Marketing Organization
- Jul 27, 2012
Unichem — Marketing Organization
- Jan 1, 2015
Earliest Phase 1 Sponsor(trial)
- Jan 1, 2015
Earliest Phase 3 Sponsor(trial)
Indications
Studied for
- Arthroplasty · Phase 4
- Colonic Neoplasms · Phase 4
- Constipation · Phase 4
- Diverticulitis, Colonic · Phase 4
- Drug-Related Side Effects and Adverse Reactions · Phase 4
- Ileus · Phase 4
- Intestinal Pseudo-Obstruction · Phase 4
- Ligaments · Phase 4
- Liver Cirrhosis · Phase 3
- Low Back Pain · Phase 4
- Muscle Cramp · Phase 3
- Osteoarthritis · Early Phase 1
- Pain · Phase 4
- Pain Management · Phase 4
- Postoperative Pain · Phase 4
- Rectal Neoplasms · Phase 4
- Spinal Fusion · Phase 4
Mechanism of action
- Histamine H1 receptorANTAGONIST
HRH1 antagonist
- Glutamate [NMDA] receptorANTAGONIST
Glutamate [NMDA] receptor antagonist
- Glutamate receptor ionotropic, NMDA 1 (GRIN1) ↗
- Glutamate receptor ionotropic, NMDA 2A (GRIN2A) ↗
- Glutamate receptor ionotropic, NMDA 2B (GRIN2B) ↗
- Glutamate receptor ionotropic, NMDA 2D (GRIN2D) ↗
- Glutamate receptor ionotropic, NMDA 3B (GRIN3B) ↗
- Glutamate receptor ionotropic, NMDA 2C (GRIN2C) ↗
- Glutamate receptor ionotropic, NMDA 3A (GRIN3A) ↗
- Glutamate (NMDA) receptor subunit zeta 1
- Glutamate [NMDA] receptor subunit epsilon 1
- Glutamate [NMDA] receptor subunit epsilon 2
- Glutamate [NMDA] receptor subunit 3A
- Glutamate [NMDA] receptor subunit epsilon 4
- Glutamate [NMDA] receptor subunit epsilon 3
- Glutamate NMDA receptor; GRIN1/GRIN2B
- Glutamate NMDA receptor; GRIN1/GRIN2A
- Ionotropic glutamate receptor NMDA 1/2C
- Ionotropic glutamate receptor NMDA 1/2D
- Glutamate NMDA receptor; GRIN1/GRIN2A/GRIN2B
- Glutamate receptor ionotropic, NMDA 1/2C/3B
- Sodium channel alpha subunitBLOCKER
Sodium channel alpha subunit blocker
- Sodium channel protein type 1 subunit alpha (SCN1A) ↗
- Sodium channel protein type 5 subunit alpha (SCN5A) ↗
- Sodium channel protein type 4 subunit alpha (SCN4A) ↗
- Sodium channel protein type 7 subunit alpha (SCN7A) ↗
- Sodium channel protein type 2 subunit alpha (SCN2A) ↗
- Sodium channel protein type 9 subunit alpha (SCN9A) ↗
- Sodium channel protein type 3 subunit alpha (SCN3A) ↗
- Sodium channel protein type 11 subunit alpha (SCN11A) ↗
- Sodium channel protein type 8 subunit alpha (SCN8A) ↗
- Sodium channel protein type 10 subunit alpha (SCN10A) ↗
- Sodium channel protein type I alpha subunit
- Sodium channel protein type V alpha subunit
- Sodium channel protein type IV alpha subunit
- Sodium channel protein type VII alpha subunit
- Sodium channel protein type IX alpha subunit
- Sodium channel protein type II alpha subunit
- Sodium channel protein type III alpha subunit
- Sodium channel protein type XI alpha subunit
- Sodium channel protein type VIII alpha subunit
- Sodium channel protein type X alpha subunit
- Sodium channel alpha subunits; brain (Types I, II, III)
- Norepinephrine transporterINHIBITOR
SLC6A2 inhibitor
Combination products
norgesic forte
with caffeine, acetylsalicylic acid
Also known as invagesic, invagesic forte, norgesic, orphengesic, orphengesic forte
Approval history
- approvedMay 10, 1957
Chemistry & pharmacology
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
- WikipediaOrphenadrine ↗
- NCATSAL805O9OG9 ↗
- ChEMBLCHEMBL900 ↗
- ChEMBLCHEMBL1201023 ↗
- ChEMBLCHEMBL1200395 ↗
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 ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT05413902 | Phase 4 | Apr 5, 2021 | University of Puerto Rico |
| NCT04509336 | N/A | May 20, 2020 | Mansoura University, Tanta University |
| NCT04835116 | Phase 4 | Apr 11, 2019 | Government of India, Government of Pakistan |
| NCT03493490 | Phase 4 | Mar 1, 2018 | Medical University of Vienna |
| NCT02985671 | Phase 3 | Jun 1, 2017 | Ache 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 |
| NCT02958566 | Phase 4 | Jan 1, 2017 | OSF HealthCare, University of Illinois |
| NCT02665286 | Phase 4 | Mar 1, 2016 | Yeshiva University |
| NCT02485145 | Early Phase 1 (Phase 1) | Jul 1, 2015 | Transdermal Therapeutics, Inc., Yeshiva University |
| NCT02449369 | Phase 4 | Apr 1, 2015 | Advent Health, Sagent Pharmaceuticals, Inc. |
| NCT02423395 | Phase 3 | Jan 1, 2015 | Tanta University |
| NCT01263652 | N/A | Dec 1, 2010 | Western Galilee Hospital |
Organizations
Research & Development (18)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Tanta University | Academic/Hospital | 2 | 1 | 2 | 2015 |
| Yeshiva University | Academic/Hospital | 2 | 1 | 2 | 2015 |
| Ache Laboratorios Farmaceuticos S.A. | For profit | 1 | 1 | 1 | 2017 |
| Advent Health | Academic/Hospital | 1 | 1 | 1 | 2015 |
| Allergisa Pesquisa Dermato-Cosmetica LTDA | For profit | 1 | 0 | 1 | 2017 |
| Association of Assistance to the Disabled Child | Academic/Hospital | 1 | 0 | 1 | 2017 |
| Center for the Development of Clinical Studies Brazil | Government | 1 | 0 | 1 | 2017 |
| Government of India | Government | 1 | 0 | 1 | 2019 |
| Government of Pakistan | Government | 1 | 1 | 1 | 2019 |
| Instituto Nacional de Traumatologia e Ortopedia | Academic/Hospital | 1 | 0 | 1 | 2017 |
| Mansoura University | Academic/Hospital | 1 | 1 | 1 | 2020 |
| Medical University of Vienna | Academic/Hospital | 1 | 1 | 1 | 2018 |
| OSF HealthCare | Academic/Hospital | 1 | 0 | 1 | 2017 |
| Sagent Pharmaceuticals, Inc. | For profit | 1 | 0 | 1 | 2015 |
| Transdermal Therapeutics, Inc. | For profit | 1 | 1 | 1 | 2015 |
| University of Illinois | Academic/Hospital | 1 | 1 | 1 | 2017 |
| University of Puerto Rico | Academic/Hospital | 1 | 1 | 1 | 2021 |
| Western Galilee Hospital | Academic/Hospital | 1 | 1 | 1 | 2010 |
Marketing (25)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| 3M | For profit | NDA2 | May 10, 1957 |
| 3M | For profit | NDA | May 10, 1957 |
| ANDA Repository | For profit | MKTG | Jan 29, 1999 |
| Akorn, Inc. | For profit | MKTG | May 24, 2006 |
| Ascot Pharmaceuticals | For profit | MKTG | — |
| Bausch Health Companies | For profit | NDA2 | Nov 4, 1959 |
| Bayshore Pharms Llc | For profit | MKTG | Jul 27, 2012 |
| Chartwell Pharmaceuticals | For profit | MKTG | Nov 27, 1996 |
| Galt Pharmaceuticals | For profit | MKTG | May 29, 1998 |
| Hikma | For profit | MKTG | Mar 4, 2003 |
| Impax Laboratories | For profit | MKTG | Jun 23, 2000 |
| Invagen Pharms | For profit | MKTG | Jul 27, 2012 |
| Jerome Stevens Pharmaceuticals | For profit | MKTG | Apr 30, 1999 |
| Lupin | For profit | MKTG | Jun 19, 1998 |
| Medicis | For profit | NDA2 | Nov 4, 1959 |
| Novartis | For profit | MKTG | Nov 27, 1996 |
| Pharmaceutical Associates | For profit | MKTG | Oct 2, 1960 |
| Pharmaceutical Associates | For profit | NDA2 | Oct 2, 1960 |
| Rising Pharmaceuticals | For profit | MKTG | Jan 29, 1999 |
| Sagent Pharmaceuticals, Inc. | For profit | MKTG | Aug 30, 2011 |
| Sandoz | For profit | MKTG | Jun 29, 1982 |
| Teligent Pharmaceuticals | For profit | NDA2 | Oct 2, 1960 |
| Unichem | For profit | MKTG | Jul 27, 2012 |
| Watson Pharmaceuticals | For profit | MKTG | Jul 16, 1981 |
| West-Ward Pharmaceutical | For profit | MKTG | Mar 4, 2003 |