Details of the Drug

General Information of Drug (ID: DMW542E)

Drug Name

Orphenadrine

Synonyms

Antiflex; Biorphen; Brocadisipal; Brocasipal; Disipal; Lysantin; Mefenamine; Mephenamine; Methyldiphenylhydramine; Myolin; Myotrol; ORP; Orfenadrina; Orfro; Orphenadine; Orphenadinum; Orphenadrin; Orphenadrinum; Orphenate; Orphenedrine; Norflex Orphenadrine Citrate; Sodium Mefenamine; WS 2434; Banflex (TN); Biorphen (TN); Brocasipal (TN); Disipal (TN); Flexon (TN); Mephenamin (TN); Mialgin (TN); Norflex (TN); O-Methyldiphenhydramine; O-Monomethyldiphenhydramine; Orfenadrina [INN-Spanish]; Orphenadrine(INN); Orphenadrine [INN:BAN]; Orphenadrinum [INN-Latin]; Beta-Dimethylaminoethyl 2-methylbenzhydryl ether; Phenyl-o-tolylmethyl dimethyaminoethyl ether; Beta-Dimethylaminoethyl-2-methylbenzhydryl ether; N,N-Dimethyl-2-(alpha-2-tolylbenzoyloxy)ethylamin; N,N-Dimethyl-2-[(2-methylphenyl)(phenyl)methoxy]ethanamine; N,N-dimethyl-2-(alpha-2-tolylbenzoyloxy)ethylamine; N,N-dimethyl-2-[(2-methylphenyl)-phenylmethoxy]ethanamine; N,N-Dimethyl-2-(o-methyl-alpha-phenylbenzyl)oxy)ethylamine; N,N-Dimethyl-2-[(o-methyl-alpha-phenylbenzyl)oxy]ethylamine; N,N-dimethyl-2-{[(2-methylphenyl)(phenyl)methyl]oxy}ethanamine; 2-(Phenyl-o-tolylmethoxy)ethyldimethylamine; 2-Methyldiphenhydramine

Indication

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Approved	[1], [2]

Therapeutic Class

Antiparkinson Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

269.4

Topological Polar Surface Area (xlogp)

3.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Bioavailability: 90% of drug becomes completely available to its intended biological destination(s) [4]
Elimination: 8% of drug is excreted from urine in the unchanged form [3]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 21.2119 micromolar/kg/day [5]
Water Solubility: The ability of drug to dissolve in water is measured as 10 mg/mL [3]

Chemical Identifiers

Formula: C18H23NO
IUPAC Name: N,N-dimethyl-2-[(2-methylphenyl)-phenylmethoxy]ethanamine
Canonical SMILES: CC1=CC=CC=C1C(C2=CC=CC=C2)OCCN(C)C
InChI: 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
InChIKey: QVYRGXJJSLMXQH-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 4601
ChEBI ID: CHEBI:7789
CAS Number: 83-98-7
DrugBank ID: DB01173
TTD ID: D0D9FV
VARIDT ID: DR00835
ACDINA ID: D00492

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
N-methyl-D-aspartate receptor (NMDAR)	TT9IK2Z	NOUNIPROTAC	Antagonist	[6], [7]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Orphenadrine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Oliceridine	DM6MDCF	Major	Additive CNS depression effects by the combination of Orphenadrine and Oliceridine.	Acute pain [MG31]	[18]
Mepyramine	DMB4SFH	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Mepyramine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[19]
Acetylcholine	DMDF79Z	Moderate	Antagonize the effect of Orphenadrine when combined with Acetylcholine.	Cataract [9B10]	[20]
Umeclidinium	DM4E8O9	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Umeclidinium.	Chronic obstructive pulmonary disease [CA22]	[21]
Tiotropium	DMFDC0Q	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Tiotropium.	Chronic obstructive pulmonary disease [CA22]	[21]
Revefenacin	DMMP5SI	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[21]
Dihydrocodeine	DMB0FWL	Major	Additive CNS depression effects by the combination of Orphenadrine and Dihydrocodeine.	Chronic pain [MG30]	[22]
Clomipramine	DMINRKW	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Clomipramine.	Depression [6A70-6A7Z]	[23]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Orphenadrine and Esketamine.	Depression [6A70-6A7Z]	[24]
Mepenzolate	DM8YU2F	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Mepenzolate.	Digestive system disease [DE2Z]	[23]
Solifenacin	DMG592Q	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Solifenacin.	Functional bladder disorder [GC50]	[23]
Belladonna	DM2RBWK	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[23]
ITI-007	DMUQ1DO	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and ITI-007.	Insomnia [7A00-7A0Z]	[23]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Orphenadrine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[25]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Orphenadrine and Lasmiditan.	Migraine [8A80]	[26]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Orphenadrine and Flibanserin.	Mood disorder [6A60-6E23]	[27]
Phenindamine	DMDTC7R	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Phenindamine.	Nasopharyngitis [CA00]	[23]
Cyclizine	DM9G7BS	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Cyclizine.	Nausea/vomiting [MD90]	[23]
Levomethadyl Acetate	DM06HG5	Major	Additive CNS depression effects by the combination of Orphenadrine and Levomethadyl Acetate.	Opioid use disorder [6C43]	[22]
Oxymorphone	DM65AGJ	Major	Additive CNS depression effects by the combination of Orphenadrine and Oxymorphone.	Pain [MG30-MG3Z]	[18]
Dezocine	DMJDB0Y	Major	Additive CNS depression effects by the combination of Orphenadrine and Dezocine.	Pain [MG30-MG3Z]	[18]
Methylscopolamine	DM5VWOB	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Methylscopolamine.	Peptic ulcer [DA61]	[23]
Levomepromazine	DMIKFEL	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Levomepromazine.	Psychotic disorder [6A20-6A25]	[23]
Quetiapine	DM1N62C	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Quetiapine.	Schizophrenia [6A20]	[23]
Aripiprazole	DM3NUMH	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Aripiprazole.	Schizophrenia [6A20]	[23]
Iloperidone	DM6AUFY	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Iloperidone.	Schizophrenia [6A20]	[23]
Paliperidone	DM7NPJS	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Paliperidone.	Schizophrenia [6A20]	[23]
Molindone	DMAH70G	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Molindone.	Schizophrenia [6A20]	[23]
Thiothixene	DMDINC4	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Thiothixene.	Schizophrenia [6A20]	[23]
Asenapine	DMSQZE2	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Asenapine.	Schizophrenia [6A20]	[23]
Trimeprazine	DMEMV9D	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Trimeprazine.	Vasomotor/allergic rhinitis [CA08]	[19]
Acrivastine	DMTIGA0	Moderate	Additive anticholinergic effects by the combination of Orphenadrine and Acrivastine.	Vasomotor/allergic rhinitis [CA08]	[23]
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⏷ Show the Full List of 32 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Calcium stearate	E00244	15324	lubricant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Orphenadrine 100 mg tablet	100 mg	12 HR Extended Release Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7251).
2	FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040249.
3	BDDCS applied to over 900 drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	Involvement of voltage-gated sodium channels blockade in the analgesic effects of orphenadrine. Pain. 2009 Apr;142(3):225-35.
7	Dopamine/glutamate interactions in Parkinson's disease. Neurosci Biobehav Rev. 1997 Jul;21(4):393-400.
8	Altered expression of genes involved in GABAergic transmission and neuromodulation of granule cell activity in the cerebellum of schizophrenia pati... Am J Psychiatry. 2008 Dec;165(12):1594-603.
9	How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
10	Amphetamine inhibits the N-methyl-D-aspartate receptor-mediated responses by directly interacting with the receptor/channel complex. J Pharmacol Exp Ther. 2002 Mar;300(3):1008-16.
11	Ketamine modulates theta and gamma oscillations. J Cogn Neurosci. 2010 Jul;22(7):1452-64.
12	Molecular determinants of the anticonvulsant felbamate binding site in the N-methyl-D-aspartate receptor. J Med Chem. 2008 Mar 27;51(6):1534-45.
13	The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence. Int J Geriatr Psychiatry. 2003 Sep;18(Suppl 1):S23-32.
14	Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res. 2009 Jan;83(1):1-43.
15	Neuroprotective agents for the treatment of acute ischemic stroke. Curr Neurol Neurosci Rep. 2003 Jan;3(1):9-20.
16	Magnesium sulfate diminishes the effects of amide local anesthetics in rat sciatic-nerve block. Reg Anesth Pain Med. 2007 Jul-Aug;32(4):288-95.
17	Emerging drugs for acute ischemic stroke. Expert Opin Emerg Drugs. 2009 Mar;14(1):33-42.
18	US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
19	Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82. [PMID: 7202232]
20	Multum Information Services, Inc. Expert Review Panel.
21	Cole JM, Sheehan AH, Jordan JK "Concomitant use of ipratropium and tiotropium in chronic obstructive plmonary disease." Ann Pharmacother 46 (2012): 1717-21. [PMID: 23170031]
22	US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
23	Cohen MA, Alfonso CA, Mosquera M. Development of urinary retention during treatment with clozapine and meclizine [published correction appears in Am J Psychiatry 1994 Jun;151(6):952]. Am J Psychiatry. 1994;151(4):619-620. [PMID: 8147469]
24	Cerner Multum, Inc. "Australian Product Information.".
25	Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
26	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
27	Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.