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Details

Stereochemistry RACEMIC
Molecular Formula C18H23NO
Molecular Weight 269.382
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ORPHENADRINE

SMILES

Cc1ccccc1C(c2ccccc2)OCCN(C)C

InChI

InChIKey=QVYRGXJJSLMXQH-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C18H23NO
Molecular Weight 269.382
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html

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class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs.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

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
97.7 µM [IC50]
6.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DISIPAL

Approved Use

Orphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions.

Launch Date

-3.99081603E11
Primary
DISIPAL

Approved Use

Orphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions.

Launch Date

-3.99081603E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
41.89 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
49.19 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1739.15 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1772.44 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.02 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
22.29 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
7%
ORPHENADRINE plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
500 mg 1 times / day steady, oral
Highest studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: steady
Dose: 500 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: depression
Age Group: adult
Sources:
2 g single, intramuscular
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
2 g single, intravenous
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
2 g single, oral
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
AEs
PubMed

PubMed

TitleDatePubMed
[Pilot study on the effects of an antiparkinson anticholinergic agent during depressive conditions].
1975
Prochlorperazine in childhood: side-effects.
1977
Reversal of orphenadrine-induced ventricular tachycardia with physostigmine.
1991 Nov-Dec
In vitro long-term cytotoxicity testing of 27 MEIC chemicals on Hep G2 cells and comparison with acute human toxicity data.
2001 Apr
Orphenadrine prevents 3-nitropropionic acid-induced neurotoxicity in vitro and in vivo.
2001 Feb
Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes.
2001 Jun
Involvement of human liver cytochrome P4502B6 in the metabolism of propofol.
2001 Mar
Acute intoxication with orphenadrine and clozapine.
2001 Nov 15
Non-sustained ventricular tachycardia due to low-dose orphenadrine.
2001 Oct 1
Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity.
2002
Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes.
2002 Jul
Spectrophotometric determination of phenylephrine HCl and orphenadrine citrate in pure and in dosage forms.
2002 Nov 7
Therapeutic response of benzodiazepine, orphenadrine citrate and occlusal splint association in TMD pain.
2003 Apr
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Cytochrome P-4503A1 catalyzes the formation of MA1 from territrem a in liver microsomes of 7-week-old female Wistar rats.
2003 Mar 14
Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats.
2003 Nov
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.
2003 Nov 17
300-Hz subthalamic oscillations in Parkinson's disease.
2003 Oct
[Diclofenac 75mg. and 30 mg. orfenadine (Neodolpasse) versus placebo and piroxicam in postoperative analgesia after arthroscopy].
2004
Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer.
2004 Jan 12
Validated semiquantitative/quantitative screening of 51 drugs in whole blood as silylated derivatives by gas chromatography-selected ion monitoring mass spectrometry and gas chromatography electron capture detection.
2004 Jul 5
NMDA receptor in nucleus accumbens is implicated in morphine withdrawal in rats.
2004 Nov
Primary chemotherapy with gemcitabine, epirubicin and taxol (GET) in operable breast cancer: a phase II study.
2005 Aug 22
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A.
2005 Feb 27
Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid-phase extraction and gas chromatography/mass spectrometry.
2006
Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune diabetes: focus on the choice of anti-H1 drugs.
2006 Dec
Pharmacokinetic study of orphenadrine using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
2006 Jul 24
A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer.
2006 May 24
OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice.
2006 Nov
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.
2008 Dec
Are there alternatives to the use of quinine to treat nocturnal leg cramps?
2008 Feb
Effects of CYP inducers and inhibitors on the pharmacokinetics of intravenous theophylline in rats: involvement of CYP1A1/2 in the formation of 1,3-DMU.
2008 Jan
Evaluation of luciferin-isopropyl acetal as a CYP3A4 substrate for human hepatocytes: effects of organic solvents, cytochrome P450 (P450) inhibitors, and P450 inducers.
2009 Aug
The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study.
2009 Feb
Effects of cytochrome P450 inducers and inhibitors on the pharmacokinetics of intravenous furosemide in rats: involvement of CYP2C11, 2E1, 3A1 and 3A2 in furosemide metabolism.
2009 Jan
Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders.
2009 Jun 3
Physiological and pathological role of alpha-synuclein in Parkinson's disease through iron mediated oxidative stress; the role of a putative iron-responsive element.
2009 Mar
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
Testosterone hydroxylation in bovine liver: enzyme kinetic and inhibition study.
2010 Apr
Orphenadrinium picrate picric acid.
2010 Feb 24
(2-Methyl-phen-yl)(phen-yl)methanol.
2010 Jul 31
Pharmacologic management of chronic pain.
2010 Jun
7-Benzyloxyresorufin-O-dealkylase activity as a marker for measuring cytochrome P450 CYP3A induction in mouse liver.
2010 Mar 1
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Patents

Patents

Sample Use Guides

Acute musculoskeletal conditions: 100 mg orally twice a day (morning and evening) or 60 mg by intramuscular or intravenous injection. May repeat every 12 hours. Quinine-resistant leg cramps: 100 mg orally at bedtime.
Route of Administration: Other
In Vitro Use Guide
An aliquot (400 mkl) of the brain membrane suspension (0.14 mg of protein), 100 mkl of (-)3H-QNB (0.95 nM) (specific activity 46 Ci/mmol), and 50 mk1 of the competing drugs at various concentrations were preincubated for 10 min. and thereafter incubated for 60 min. at 25C in 50 mM Tris-HC1 buffer (PH 7.4). When binding to heart and lung membranes was studied, 500 nkl of homogenate (protein contents were 0.58 mg and 0.54 mg of rat heart and lung tissue and 0.63 mg of guinea pig lung tissue was added to tubes containing 500 mkl of 50 mM Tris-HC1 buffer (PH 7.4), 100 mk1 of (-)3H-QNB (final concentration 0.4 nM) and 100 mkl of buffer (total binding) or unlabeled Orphenadrine.
Substance Class Chemical
Created
by admin
on Sat Jun 26 04:36:16 UTC 2021
Edited
by admin
on Sat Jun 26 04:36:16 UTC 2021
Record UNII
AL805O9OG9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ORPHENADRINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
ORPHENADRIN
Common Name English
ORPHENADRINE [HSDB]
Common Name English
ORPHENADRINE [MI]
Common Name English
(+/-)-N,N-DIMETHYL-2-((O-METHYL-.ALPHA.-PHENYLBENZYL)OXY)ETHYLAMINE
Common Name English
ORPHENADRINE [INN]
Common Name English
ORPHENADRINE [WHO-DD]
Common Name English
ETHANAMINE, N,N-DIMETHYL-2-((2-METHYLPHENYL)PHENYLMETHOXY)-, (+/-)-
Systematic Name English
MEFENAMINE [JAN]
Common Name English
ORPHENADRINE [VANDF]
Common Name English
MIALGIN
Brand Name English
MEFENAMINE
JAN  
Common Name English
Classification Tree Code System Code
WHO-ATC M03BC51
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
WHO-ATC N04AB02
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
WHO-VATC QM03BC01
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
WHO-VATC QM03BC51
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
NCI_THESAURUS C29704
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
LIVERTOX 715
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
NDF-RT N0000175737
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
NDF-RT N0000175730
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
WHO-ATC M03BC01
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
NCI_THESAURUS C29696
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
Code System Code Type Description
CAS
83-98-7
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
EVMPD
SUB09471MIG
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
LACTMED
Orphenadrine
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
ChEMBL
CHEMBL900
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
NCI_THESAURUS
C61868
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
DRUG BANK
DB01173
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
FDA UNII
AL805O9OG9
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
RXCUI
7715
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY RxNorm
EPA CompTox
83-98-7
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
WIKIPEDIA
ORPHENADRINE
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
IUPHAR
7251
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
MERCK INDEX
M8245
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY Merck Index
PUBCHEM
4601
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
DRUG CENTRAL
1999
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
HSDB
3139
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
ECHA (EC/EINECS)
201-509-2
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
MESH
D009966
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
INN
658
Created by admin on Sat Jun 26 04:36:16 UTC 2021 , Edited by admin on Sat Jun 26 04:36:16 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC