Midodrine - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (3)Enzymes (1)Transporters (1)

Targets (3)Enzymes (1)Transporters (1)Biointeractions (4)

Identification

Name

Midodrine

Accession Number

DB00211 (APRD01116)

Type

Small Molecule

Groups

Approved

Description

An ethanolamine derivative that is an adrenergic alpha agonist. It is used as a vasoconstrictor agent in the treatment of hypotension. [PubChem]

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

(+-)-2-amino-N-(beta-hydroxy-2,5-dimethoxyphenethyl)acetamide

1-(2',5'-Dimethoxyphenyl)-2-glycinamidoethanol

2-Amino-N-(2,5-dimethoxy-beta-hydroxyphenethyl)acetamide

DL-N1-(beta-Hydroxy-2,5-dimethoxyphenethyl)glycinamid

Midodrin

Midodrina

Midodrinum

External IDs

Not Available

Product Ingredients

Ingredient	UNII	CAS	InChI Key	Details
Midodrine hydrochloride	59JV96YTXV	43218-56-0	MGCQZNBCJBRZDT-UHFFFAOYNA-N	Details

Product Images

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Amatine	Tablet	2.5 mg	Oral	Shire Pharma Canada Ulc	1992-12-31	2010-09-30	Canada
Amatine	Tablet	5 mg	Oral	Shire Pharma Canada Ulc	1992-12-31	2010-10-04	Canada
Midodrine	Tablet	2.5 mg	Oral	Aa Pharma Inc	2006-06-13	Not applicable	Canada
Midodrine	Tablet	5.0 mg	Oral	Aa Pharma Inc	2006-06-13	Not applicable	Canada
Proamatine	Tablet	2.5 mg/1	Oral	Shire	1996-09-06	Not applicable	US
Proamatine	Tablet	5 mg/1	Oral	Physicians Total Care, Inc.	2005-09-30	Not applicable	US
Proamatine	Tablet	5 mg/1	Oral	Shire	1996-09-06	Not applicable	US
Proamatine	Tablet	10 mg/1	Oral	Shire	2002-03-20	Not applicable	US

Approved Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Midodrine HCl	Tablet	5 mg/1	Oral	Eon Labs, Inc.	2003-09-11	Not applicable	US
Midodrine HCl	Tablet	5 mg/1	Oral	Mc Kesson Packaging Services A Buisness Unit Of Mc Kesson Corporation	2012-11-26	Not applicable	US
Midodrine HCl	Tablet	10 mg/1	Oral	Rebel Distributors	2002-07-02	Not applicable	US
Midodrine HCl	Tablet	5 mg/1	Oral	Cardinal Health	2004-11-03	2017-05-05	US
Midodrine HCl	Tablet	10 mg/1	Oral	Eon Labs, Inc.	2002-07-02	Not applicable	US
Midodrine HCl	Tablet	2.5 mg/1	Oral	Amerincan Health Packaging	2010-05-11	Not applicable	US
Midodrine HCl	Tablet	5 mg/1	Oral	Cardinal Health	2012-11-26	Not applicable	US
Midodrine HCl	Tablet	2.5 mg/1	Oral	Eon Labs, Inc.	2003-09-11	Not applicable	US
Midodrine HCl	Tablet	5 mg/1	Oral	Amerincan Health Packaging	2010-05-11	Not applicable	US
Midodrine HCl	Tablet	5 mg/1	Oral	Cardinal Health	2004-11-03	Not applicable	US
Midodrine HCl	Tablet	2.5 mg/1	Oral	Cardinal Health	2010-05-11	Not applicable	US
Midodrine Hydrochloride	Tablet	2.5 mg/1	Oral	Av Kare, Inc.	2017-05-05	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Ncs Health Care Of Ky, Inc Dba Vangard Labs	2003-09-10	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Apotex Corporation	2006-09-12	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Cardinal Health	2011-01-14	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Physicians Total Care, Inc.	2006-01-01	Not applicable	US
Midodrine Hydrochloride	Tablet	10 mg/1	Oral	Amerincan Health Packaging	2015-09-01	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Mylan Pharmaceuticals	2003-09-11	Not applicable	US
Midodrine Hydrochloride	Tablet	10 mg/1	Oral	Impax Generics	2005-12-16	Not applicable	US
Midodrine Hydrochloride	Tablet	2.5 mg/1	Oral	Apotex Corporation	2006-09-12	Not applicable	US
Midodrine Hydrochloride	Tablet	10 mg/1	Oral	bryant ranch prepack	2003-09-11	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Av Pak	2011-08-17	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Carilion Materials Management	2004-05-27	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Upsher Smith Laboratories	2004-11-03	Not applicable	US
Midodrine Hydrochloride	Tablet	2.5 mg/1	Oral	Physicians Total Care, Inc.	2008-08-19	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Av Kare, Inc.	2017-05-05	Not applicable	US
Midodrine Hydrochloride	Tablet	10 mg/1	Oral	Ncs Health Care Of Ky, Inc Dba Vangard Labs	2003-09-10	Not applicable	US
Midodrine Hydrochloride	Tablet	10 mg/1	Oral	Apotex Corporation	2006-09-12	Not applicable	US
Midodrine Hydrochloride	Tablet	2.5 mg/1	Oral	Impax Generics	2004-05-27	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Av Kare, Inc.	2004-05-27	Not applicable	US
Midodrine Hydrochloride	Tablet	2.5 mg/1	Oral	Avera Mc Kennan Hospital	2015-03-01	Not applicable	US
Midodrine Hydrochloride	Tablet	10 mg/1	Oral	Mylan Pharmaceuticals	2003-09-11	Not applicable	US
Midodrine Hydrochloride	Tablet	10 mg/1	Oral	Av Pak	2011-08-17	Not applicable	US
Midodrine Hydrochloride	Tablet	10 mg/1	Oral	Upsher Smith Laboratories	2004-11-03	Not applicable	US
Midodrine Hydrochloride	Tablet	2.5 mg/1	Oral	Mylan Pharmaceuticals	2003-09-11	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Impax Generics	2004-05-27	Not applicable	US
Midodrine Hydrochloride	Tablet	5 mg/1	Oral	Mylan Institutional	2006-09-11	Not applicable	US
Midodrine Hydrochloride	Tablet	10 mg/1	Oral	Av Kare, Inc.	2017-05-05	Not applicable	US
Midodrine Hydrochloride	Tablet	2.5 mg/1	Oral	Ncs Health Care Of Ky, Inc Dba Vangard Labs	2003-09-10	Not applicable	US
Midodrine Hydrochloride	Tablet	2.5 mg/1	Oral	Av Pak	2011-08-17	Not applicable	US
Midodrine Hydrochloride	Tablet	2.5 mg/1	Oral	Upsher Smith Laboratories	2004-11-03	Not applicable	US

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Not Available

Brand mixtures

Not Available

Categories

UNII

6YE7PBM15H

CAS number

42794-76-3

Weight

Average: 254.2823
Monoisotopic: 254.126657074

Chemical Formula

C₁₂H₁₈N₂O₄

InChI Key

PTKSEFOSCHHMPD-UHFFFAOYSA-N

InChI

InChI=1S/C12H18N2O4/c1-17-8-3-4-11(18-2)9(5-8)10(15)7-14-12(16)6-13/h3-5,10,15H,6-7,13H2,1-2H3,(H,14,16)

IUPAC Name

2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]acetamide

SMILES

COC1=CC(C(O)CNC(=O)CN)=C(OC)C=C1

Pharmacology

Indication

For the treatment of symptomatic orthostatic hypotension (OH).

Structured Indications

Symptomatic Orthostatic Hypotension

Pharmacodynamics

Midodrine is a prodrug, i.e., the therapeutic effect of orally administered midodrine is due to the major metabolite desglymidodrine formed by deglycination of midodrine. Desglymidodrine diffuses poorly across the blood-brain barrier, and is therefore not associated with effects on the central nervous system. Administration of midodrine results in a rise in standing, sitting, and supine systolic and diastolic blood pressure in patients with orthostatic hypotension of various etiologies. Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10-mg dose of midodrine, with some effect persisting for 2 to 3 hours. Midodrine has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure.

Mechanism of action

Midodrine forms an active metabolite, desglymidodrine, that is an alpha₁-agonist, and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. Desglymidodrine does not stimulate cardiac beta-adrenergic receptors.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Alpha-1A adrenergic receptor	Protein	yes	agonist	Human	P35348	details
Alpha-1B adrenergic receptor	Protein	yes	agonist	Human	P35368	details
Alpha-1D adrenergic receptor	Protein	unknown	agonist	Human	P25100	details

Absorption

Rapidly absorbed following oral administration. The absolute bioavailability of midodrine (measured as desglymidodrine) is 93% and is not affected by food.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Thorough metabolic studies have not been conducted, but it appears that deglycination of midodrine to desglymidodrine takes place in many tissues, and both compounds are metabolized in part by the liver.

Substrate	Enzymes	Product
Midodrine	Not Available	desglymidodrine	Details

Route of elimination

Not Available

Half life

The plasma levels of the prodrug peak after about half an hour, and decline with a half-life of approximately 25 minutes, while the metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of midodrine and has a half-life of about 3 to 4 hours.

Clearance

Renal cl=385 mL/minute

Toxicity

Symptoms of overdose could include hypertension, piloerection (goosebumps), a sensation of coldness and urinary retention. The single doses that would be associated with symptoms of overdosage or would be potentially life- threatening are unknown. The oral LD₅₀ is approximately 30 to 50 mg/kg in rats, 675 mg/kg in mice, and 125 to 160 mg/kg in dogs. Desglymidodrine is dialyzable.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline	7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE may increase the hypertensive activities of Midodrine.	Experimental
Acebutolol	Acebutolol may increase the bradycardic activities of Midodrine.	Approved
Acetyldigitoxin	Acetyldigitoxin may increase the bradycardic activities of Midodrine.	Approved
Alfuzosin	Alfuzosin may decrease the vasoconstricting activities of Midodrine.	Approved, Investigational
Alprenolol	Alprenolol may increase the bradycardic activities of Midodrine.	Approved, Withdrawn
Amineptine	Amineptine may increase the vasopressor activities of Midodrine.	Illicit, Withdrawn
Amitriptyline	Amitriptyline may increase the vasopressor activities of Midodrine.	Approved
Amphetamine	The risk or severity of adverse effects can be increased when Amphetamine is combined with Midodrine.	Approved, Illicit
Arotinolol	Arotinolol may increase the bradycardic activities of Midodrine.	Approved
Atenolol	Atenolol may increase the bradycardic activities of Midodrine.	Approved
Atomoxetine	Atomoxetine may increase the hypertensive activities of Midodrine.	Approved
Befunolol	Befunolol may increase the bradycardic activities of Midodrine.	Experimental
Benmoxin	Benmoxin may increase the hypertensive activities of Midodrine.	Withdrawn
Benzphetamine	The risk or severity of adverse effects can be increased when Midodrine is combined with Benzphetamine.	Approved, Illicit
Benzylpenicilloyl Polylysine	Midodrine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.	Approved
Betaxolol	Betaxolol may increase the bradycardic activities of Midodrine.	Approved
Bevantolol	Bevantolol may increase the bradycardic activities of Midodrine.	Approved
Bisoprolol	Bisoprolol may increase the bradycardic activities of Midodrine.	Approved
Bopindolol	Bopindolol may increase the bradycardic activities of Midodrine.	Approved
Bromocriptine	Bromocriptine may increase the hypertensive activities of Midodrine.	Approved, Investigational
Bucindolol	Bucindolol may increase the bradycardic activities of Midodrine.	Investigational
Bufuralol	Bufuralol may increase the bradycardic activities of Midodrine.	Experimental, Investigational
Bupranolol	Bupranolol may increase the bradycardic activities of Midodrine.	Approved
Cabergoline	Cabergoline may increase the hypertensive activities of Midodrine.	Approved
Caroxazone	Caroxazone may increase the hypertensive activities of Midodrine.	Withdrawn
Carteolol	Carteolol may increase the bradycardic activities of Midodrine.	Approved
Carvedilol	Carvedilol may increase the bradycardic activities of Midodrine.	Approved, Investigational
Celiprolol	Celiprolol may increase the bradycardic activities of Midodrine.	Approved, Investigational
Chlorphentermine	The risk or severity of adverse effects can be increased when Midodrine is combined with Chlorphentermine.	Illicit, Withdrawn
Clenbuterol	The risk or severity of adverse effects can be increased when Midodrine is combined with Clenbuterol.	Approved, Vet Approved
Clomipramine	Clomipramine may increase the vasopressor activities of Midodrine.	Approved, Vet Approved
Cyclobenzaprine	Cyclobenzaprine may increase the vasopressor activities of Midodrine.	Approved
Desipramine	Desipramine may increase the vasopressor activities of Midodrine.	Approved
Deslanoside	Deslanoside may increase the bradycardic activities of Midodrine.	Approved
Desvenlafaxine	Desvenlafaxine may increase the tachycardic activities of Midodrine.	Approved
Digitoxin	Digitoxin may increase the bradycardic activities of Midodrine.	Approved
Digoxin	Digoxin may increase the bradycardic activities of Midodrine.	Approved
Dihydroergotamine	Dihydroergotamine may increase the hypertensive activities of Midodrine.	Approved
Diltiazem	Diltiazem may increase the bradycardic activities of Midodrine.	Approved
Dobutamine	The risk or severity of adverse effects can be increased when Midodrine is combined with Dobutamine.	Approved
Dopamine	The risk or severity of adverse effects can be increased when Midodrine is combined with Dopamine.	Approved
Dosulepin	Dosulepin may increase the vasopressor activities of Midodrine.	Approved
Doxazosin	Doxazosin may decrease the vasoconstricting activities of Midodrine.	Approved
Doxepin	Doxepin may increase the vasopressor activities of Midodrine.	Approved
Doxofylline	The risk or severity of adverse effects can be increased when Midodrine is combined with Doxofylline.	Approved
Dronabinol	Dronabinol may increase the tachycardic activities of Midodrine.	Approved, Illicit
Droxidopa	Midodrine may increase the hypertensive activities of Droxidopa.	Approved, Investigational
Duloxetine	Duloxetine may increase the tachycardic activities of Midodrine.	Approved
Ephedrine	The risk or severity of adverse effects can be increased when Midodrine is combined with Ephedrine.	Approved
Epinephrine	The risk or severity of adverse effects can be increased when Midodrine is combined with Epinephrine.	Approved, Vet Approved
Ergoloid mesylate	Ergoloid mesylate may increase the hypertensive activities of Midodrine.	Approved
Ergonovine	Ergonovine may increase the hypertensive activities of Midodrine.	Approved
Ergotamine	Ergotamine may increase the hypertensive activities of Midodrine.	Approved
Esmirtazapine	Esmirtazapine may increase the vasopressor activities of Midodrine.	Investigational
Esmolol	Esmolol may increase the bradycardic activities of Midodrine.	Approved
Etilefrine	The risk or severity of adverse effects can be increased when Midodrine is combined with Etilefrine.	Withdrawn
Fenoterol	The risk or severity of adverse effects can be increased when Midodrine is combined with Fenoterol.	Approved
Fentanyl	The serum concentration of Fentanyl can be decreased when it is combined with Midodrine.	Approved, Illicit, Investigational, Vet Approved
Fesoterodine	The serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Midodrine.	Approved
Furazolidone	Furazolidone may increase the hypertensive activities of Midodrine.	Approved, Vet Approved
Hyaluronidase	Hyaluronidase may increase the vasoconstricting activities of Midodrine.	Approved, Investigational
Hydracarbazine	Hydracarbazine may increase the hypertensive activities of Midodrine.	Experimental
Hydroxyamphetamine	The risk or severity of adverse effects can be increased when Midodrine is combined with Hydroxyamphetamine hydrobromide.	Approved
Imipramine	Imipramine may increase the vasopressor activities of Midodrine.	Approved
Indenolol	Indenolol may increase the bradycardic activities of Midodrine.	Withdrawn
Indoramin	Indoramin may decrease the vasoconstricting activities of Midodrine.	Withdrawn
Iobenguane	The therapeutic efficacy of Iobenguane can be decreased when used in combination with Midodrine.	Approved
Iproclozide	Iproclozide may increase the hypertensive activities of Midodrine.	Withdrawn
Iproniazid	Iproniazid may increase the hypertensive activities of Midodrine.	Withdrawn
Isocarboxazid	Isocarboxazid may increase the hypertensive activities of Midodrine.	Approved
Isoprenaline	The risk or severity of adverse effects can be increased when Midodrine is combined with Isoprenaline.	Approved
Isoxsuprine	The risk or severity of adverse effects can be increased when Midodrine is combined with Isoxsuprine.	Approved, Withdrawn
Labetalol	Labetalol may increase the bradycardic activities of Midodrine.	Approved
Landiolol	Aop200704 may increase the bradycardic activities of Midodrine.	Investigational
Levobunolol	Levobunolol may increase the bradycardic activities of Midodrine.	Approved
Levomilnacipran	Levomilnacipran may increase the tachycardic activities of Midodrine.	Approved
Linezolid	Linezolid may increase the hypertensive activities of Midodrine.	Approved, Investigational
Mebanazine	Mebanazine may increase the hypertensive activities of Midodrine.	Withdrawn
Mephentermine	The risk or severity of adverse effects can be increased when Midodrine is combined with Mephentermine.	Approved
Metaraminol	The risk or severity of adverse effects can be increased when Midodrine is combined with Metaraminol.	Approved, Investigational
Methamphetamine	The risk or severity of adverse effects can be increased when Midodrine is combined with Methamphetamine.	Approved, Illicit
Methoxamine	The risk or severity of adverse effects can be increased when Midodrine is combined with Methoxamine.	Approved
Methylene blue	Methylene blue may increase the hypertensive activities of Midodrine.	Investigational
Metipranolol	Metipranolol may increase the bradycardic activities of Midodrine.	Approved
Metoprolol	The serum concentration of Metoprolol can be increased when it is combined with Midodrine.	Approved, Investigational
Milnacipran	Milnacipran may increase the tachycardic activities of Midodrine.	Approved
Minaprine	Minaprine may increase the hypertensive activities of Midodrine.	Approved
Mirtazapine	Mirtazapine may increase the vasopressor activities of Midodrine.	Approved
Moclobemide	Moclobemide may increase the hypertensive activities of Midodrine.	Approved
Nabilone	Nabilone may increase the tachycardic activities of Midodrine.	Approved, Investigational
Nadolol	Nadolol may increase the bradycardic activities of Midodrine.	Approved
Nialamide	Nialamide may increase the hypertensive activities of Midodrine.	Withdrawn
Norepinephrine	The risk or severity of adverse effects can be increased when Midodrine is combined with Norepinephrine.	Approved
Nortriptyline	Nortriptyline may increase the vasopressor activities of Midodrine.	Approved
Octamoxin	Octamoxin may increase the hypertensive activities of Midodrine.	Withdrawn
Oleandrin	Anvirzel may increase the bradycardic activities of Midodrine.	Experimental
Opipramol	Opipramol may increase the vasopressor activities of Midodrine.	Investigational
Orciprenaline	The risk or severity of adverse effects can be increased when Midodrine is combined with Orciprenaline.	Approved
Ouabain	Ouabain may increase the bradycardic activities of Midodrine.	Approved
Oxprenolol	Oxprenolol may increase the bradycardic activities of Midodrine.	Approved
Oxymetazoline	The risk or severity of adverse effects can be increased when Midodrine is combined with Oxymetazoline.	Approved
Pargyline	Pargyline may increase the hypertensive activities of Midodrine.	Approved
Penbutolol	Penbutolol may increase the bradycardic activities of Midodrine.	Approved, Investigational
Phenelzine	Phenelzine may increase the hypertensive activities of Midodrine.	Approved
Pheniprazine	Pheniprazine may increase the hypertensive activities of Midodrine.	Withdrawn
Phenmetrazine	The risk or severity of adverse effects can be increased when Midodrine is combined with Phenmetrazine.	Approved, Illicit
Phenoxypropazine	Phenoxypropazine may increase the hypertensive activities of Midodrine.	Withdrawn
Phentermine	The risk or severity of adverse effects can be increased when Phentermine is combined with Midodrine.	Approved, Illicit
Phenylephrine	The risk or severity of adverse effects can be increased when Midodrine is combined with Phenylephrine.	Approved
Phenylpropanolamine	The risk or severity of adverse effects can be increased when Midodrine is combined with Phenylpropanolamine.	Approved, Vet Approved, Withdrawn
Pindolol	Pindolol may increase the bradycardic activities of Midodrine.	Approved
Pirlindole	Pirlindole may increase the hypertensive activities of Midodrine.	Approved
Pivhydrazine	Pivhydrazine may increase the hypertensive activities of Midodrine.	Withdrawn
Practolol	Practolol may increase the bradycardic activities of Midodrine.	Approved
Prazosin	Prazosin may decrease the vasoconstricting activities of Midodrine.	Approved
Procaterol	The risk or severity of adverse effects can be increased when Midodrine is combined with Procaterol.	Approved
Propranolol	Propranolol may increase the bradycardic activities of Midodrine.	Approved, Investigational
Protriptyline	Protriptyline may increase the vasopressor activities of Midodrine.	Approved
Pseudoephedrine	The risk or severity of adverse effects can be increased when Midodrine is combined with Pseudoephedrine.	Approved
Rasagiline	Rasagiline may increase the hypertensive activities of Midodrine.	Approved
Ritodrine	The risk or severity of adverse effects can be increased when Midodrine is combined with Ritodrine.	Approved
Safrazine	Safrazine may increase the hypertensive activities of Midodrine.	Withdrawn
Selegiline	Selegiline may increase the hypertensive activities of Midodrine.	Approved, Investigational, Vet Approved
Silodosin	Silodosin may decrease the vasoconstricting activities of Midodrine.	Approved
Sotalol	Sotalol may increase the bradycardic activities of Midodrine.	Approved
Spironolactone	Spironolactone may decrease the vasoconstricting activities of Midodrine.	Approved
Synephrine	The risk or severity of adverse effects can be increased when Midodrine is combined with Synephrine.	Experimental
Tamsulosin	Tamsulosin may decrease the vasoconstricting activities of Midodrine.	Approved, Investigational
Tedizolid Phosphate	Tedizolid Phosphate may increase the hypertensive activities of Midodrine.	Approved
Terazosin	Terazosin may decrease the vasoconstricting activities of Midodrine.	Approved
Terbutaline	The risk or severity of adverse effects can be increased when Midodrine is combined with Terbutaline.	Approved
Tetryzoline	The risk or severity of adverse effects can be increased when Midodrine is combined with Tetryzoline.	Approved
Thioridazine	The serum concentration of Thioridazine can be increased when it is combined with Midodrine.	Withdrawn
Tianeptine	Tianeptine may increase the vasopressor activities of Midodrine.	Approved
Timolol	Timolol may increase the bradycardic activities of Midodrine.	Approved
Toloxatone	Toloxatone may increase the hypertensive activities of Midodrine.	Approved
Trans-2-Phenylcyclopropylamine	Trans-2-Phenylcyclopropylamine may increase the hypertensive activities of Midodrine.	Experimental
Tranylcypromine	Tranylcypromine may increase the hypertensive activities of Midodrine.	Approved
Trimazosin	Trimazosin may decrease the vasoconstricting activities of Midodrine.	Experimental
Trimipramine	Trimipramine may increase the vasopressor activities of Midodrine.	Approved
Tyramine	The risk or severity of adverse effects can be increased when Midodrine is combined with Tyramine.	Investigational, Nutraceutical
Venlafaxine	Venlafaxine may increase the tachycardic activities of Midodrine.	Approved
Verapamil	Verapamil may increase the bradycardic activities of Midodrine.	Approved

Food Interactions

Take without regard to meals.

References

Synthesis Reference

Anup K. Ray, Hiren Patel, Mahendra R. Patel, "Synthesis of midodrine HCI from a novel intermediate 1-(2',5'-dimethoxyphenyl)-2-azidoethanone." U.S. Patent US6201153, issued July, 1965.

US6201153

General References

Hebenstreit G: [Treatment of hypotension caused by psychopharmacological drugs (author's transl)]. Wien Med Wochenschr. 1981 Feb 28;131(4):109-12. [PubMed:6165144 ]
Tsuda M, Terada T, Irie M, Katsura T, Niida A, Tomita K, Fujii N, Inui K: Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60. Epub 2006 Apr 5. [PubMed:16597710 ]

External Links

Resource	Link
Human Metabolome Database (HMDB)	HMDB14356
KEGG Compound	C07890
PubChem Compound	4195
PubChem Substance	46507373
ChemSpider	4050
ChEBI	6933
ChEMBL	CHEMBL1201212
Therapeutic Targets Database	DAP000229
PharmGKB	PA164749381
Drug Product Database	918
RxList	http://www.rxlist.com/cgi/generic3/midodrine.htm
Drugs.com	http://www.drugs.com/cdi/midodrine.html
Wikipedia	Midodrine

ATC Codes

C01CA17 — Midodrine

AHFS Codes

12:12.00
12:12.04

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Autonomic Failure / Idiopathic orthostatic hypotension	1
1	Completed	Not Available	Healthy Volunteers	3
1	Not Yet Recruiting	Treatment	Blood Pressures / Sepsis	1
1	Recruiting	Not Available	Autonomic Failure / Idiopathic orthostatic hypotension / Multiple System Atrophy (MSA) / Progressive autonomic failure	1
1	Recruiting	Basic Science	Autonomic Failure / Idiopathic orthostatic hypotension / Multiple System Atrophy (MSA) / Parkinson's Disease (PD) / Progressive autonomic failure	1
1, 2	Active Not Recruiting	Treatment	Chronic Orthostatic Intolerance / Tachycardia	1
2	Completed	Treatment	Acute Ischemic Stroke (AIS)	1
2	Completed	Treatment	Liver Cirrhosis / Renal Failure	1
2	Completed	Treatment	Idiopathic orthostatic hypotension / Spinal Cord Injuries (SCI)	2
2	Completed	Treatment	Idiopathic orthostatic hypotension	1
2	Recruiting	Treatment	Autonomic Dysreflexia / Autonomic Integrity / Baroreceptor Integrity / Blood Pressures / Cerebral Blood Flow / Cognitive Function / Hypotensive / Spinal Cord Injuries (SCI) / Sympathetic Integrity / Vagal Integrity	1
2	Recruiting	Treatment	Fibrosis / Hepatorenal Syndrome / Renal Failure	1
2, 3	Active Not Recruiting	Treatment	Liver Cirrhosis / Refractory/Recurrent Ascites	1
2, 3	Completed	Treatment	Refractory Ascites / Type 2 Hepatorenal Syndrome	1
3	Completed	Prevention	Postoperative Orthostatic Hypotension / Postoperative Orthostatic Intolerance	1
3	Recruiting	Treatment	Arterial Hypotension / Critical Illness	1
3	Recruiting	Treatment	Shock, Septic	1
3	Recruiting	Treatment	Spinal Cord Injuries (SCI)	1
4	Completed	Not Available	Hypothermia / Mild Cognitive Impairment (MCI) / Quadriplegia	1
4	Completed	Prevention	Gastrointestinal Bleedings / Hepatic Encephalopathy / Hyponatremias / Renal Failure / Sepsis	1
4	Completed	Treatment	Ascites / Liver Cirrhosis	1
4	Completed	Treatment	Symptomatic Orthostatic Hypotension	1
4	Completed	Treatment	Idiopathic orthostatic hypotension	3
4	Enrolling by Invitation	Treatment	Intradialytic Hypotension	1
4	Not Yet Recruiting	Supportive Care	Arterial Hypotension / Sepsis / Shock, Septic	1
4	Recruiting	Supportive Care	Hypothermia / Mild Cognitive Impairment (MCI) / Quadriplegia	1
4	Recruiting	Treatment	Orthostatic; Hypotension, Neurogenic	1
4	Recruiting	Treatment	Syncope, Vasovagal	1
4	Terminated	Treatment	Idiopathic orthostatic hypotension	1
Not Available	Completed	Not Available	Orthostatic Intolerance	1
Not Available	Completed	Treatment	Syncope	1
Not Available	Not Yet Recruiting	Treatment	Arterial Hypotension / Autonomic Dysreflexia / Baroreceptor Integrity / Blood Pressures / Cerebral Blood Flow / Idiopathic orthostatic hypotension / Spinal Cord Injuries (SCI) / Sympathetic Integrity / Vagal Integrity / Venous Occlusion Plethysmography	1
Not Available	Recruiting	Treatment	Liver Cirrhosis	1
Not Available	Recruiting	Treatment	Orthostatic Intolerance / Parkinson's Disease (PD)	1
Not Available	Terminated	Treatment	Idiopathic orthostatic hypotension	1
Not Available	Withdrawn	Not Available	Strokes	1
Not Available	Withdrawn	Treatment	Arterial Hypotension / Ascites / End Stage Liver Diseases / Liver Cirrhosis	1

Pharmacoeconomics

Manufacturers

Apotex inc etobicoke site
Impax pharmaceuticals
Mylan pharmaceuticals inc
Sandoz inc
Upsher smith laboratories inc
Shire development inc

Packagers

Actavis Group
Amerisource Health Services Corp.
Apotex Inc.
Eon Labs
Global Pharmaceuticals
Heartland Repack Services LLC
Impax Laboratories Inc.
Kaiser Foundation Hospital
Murfreesboro Pharmaceutical Nursing Supply
Mylan
Nycomed Inc.
Physicians Total Care Inc.
Rebel Distributors Corp.
Resource Optimization and Innovation LLC
Shire Inc.
UDL Laboratories
Upsher Smith Laboratories
Vangard Labs Inc.

Dosage forms

Form	Route	Strength
Tablet	Oral	5 mg
Tablet	Oral	2.5 mg
Tablet	Oral	5.0 mg
Tablet	Oral	10 mg/1
Tablet	Oral	2.5 mg/1
Tablet	Oral	5 mg/1

Prices

Unit description	Cost	Unit
Proamatine 10 mg tablet	5.91USD	tablet
Midodrine hcl 10 mg tablet	4.93USD	tablet
Proamatine 5 mg tablet	3.08USD	tablet
Midodrine hcl 5 mg tablet	2.47USD	tablet
Proamatine 2.5 mg tablet	1.53USD	tablet
Midodrine hcl 2.5 mg tablet	1.23USD	tablet
Apo-Midodrine 5 mg Tablet	0.59USD	tablet
Apo-Midodrine 2.5 mg Tablet	0.35USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	200 to 203°C	Not Available
water solubility	Soluble	Not Available
logP	-0.5	Not Available
pKa	7.8	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	4.45 mg/mL	ALOGPS
logP	-0.49	ALOGPS
logP	-0.95	ChemAxon
logS	-1.8	ALOGPS
pKa (Strongest Acidic)	13.77	ChemAxon
pKa (Strongest Basic)	8.14	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	93.81 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	66.22 m³·mol^-1	ChemAxon
Polarizability	26.65 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.7686
Blood Brain Barrier	-	0.856
Caco-2 permeable	-	0.7382
P-glycoprotein substrate	Substrate	0.784
P-glycoprotein inhibitor I	Non-inhibitor	0.9781
P-glycoprotein inhibitor II	Non-inhibitor	0.9866
Renal organic cation transporter	Non-inhibitor	0.8896
CYP450 2C9 substrate	Non-substrate	0.8519
CYP450 2D6 substrate	Non-substrate	0.7593
CYP450 3A4 substrate	Non-substrate	0.5595
CYP450 1A2 substrate	Inhibitor	0.8848
CYP450 2C9 inhibitor	Non-inhibitor	0.9385
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Inhibitor	0.8993
CYP450 3A4 inhibitor	Non-inhibitor	0.867
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9316
Ames test	Non AMES toxic	0.774
Carcinogenicity	Non-carcinogens	0.8613
Biodegradation	Not ready biodegradable	0.9595
Rat acute toxicity	2.3137 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9772
hERG inhibition (predictor II)	Non-inhibitor	0.8604

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum Type	Description	Splash Key
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available

Taxonomy

Description

This compound belongs to the class of chemical entities known as dimethoxybenzenes. These are organic aromatic compounds containing a monocyclic benzene moiety carrying exactly two methoxy groups.

Kingdom

Chemical entities

Super Class

Organic compounds

Class

Benzenoids

Sub Class

Benzene and substituted derivatives

Direct Parent

Dimethoxybenzenes

Alternative Parents

Phenoxy compounds / Anisoles / Alkyl aryl ethers / Secondary alcohols / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids / Organopnictogen compounds / Monoalkylamines / Hydrocarbon derivatives / Aromatic alcohols

Substituents

P-dimethoxybenzene / Dimethoxybenzene / Phenoxy compound / Anisole / Phenol ether / Alkyl aryl ether / Secondary alcohol / Carboximidic acid / Carboximidic acid derivative / Ether

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

aromatic ether, amino acid amide, secondary alcohol (CHEBI:6933 )

Targets

Details

1. Alpha-1A adrenergic receptor

Kind: Protein
Organism: Human
Pharmacological action: yes
Actions: agonist

General Function:: Protein heterodimerization activity
Specific Function:: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:: ADRA1A
Uniprot ID:: P35348
Molecular Weight:: 51486.005 Da

References

Buckner SA, Milicic I, Daza AV, Meyer MD, Altenbach RJ, Williams M, Sullivan JP, Brioni JD: ABT-866, a novel alpha(1A)-adrenoceptor agonist with antagonist properties at the alpha(1B)- and alpha(1D)-adrenoceptor subtypes. Eur J Pharmacol. 2002 Aug 2;449(1-2):159-65. [PubMed:12163120 ]
Taniguchi N, Hamada K, Ogasawara T, Ukai Y, Yoshikuni Y, Kimura K: NS-49, an alpha 1A-adrenoceptor agonist, selectively increases intraurethral pressure in dogs. Eur J Pharmacol. 1996 Dec 27;318(1):117-22. [PubMed:9007522 ]
Altenbach RJ, Khilevich A, Kolasa T, Rohde JJ, Bhatia PA, Patel MV, Searle XB, Yang F, Bunnelle WH, Tietje K, Bayburt EK, Carroll WA, Meyer MD, Henry R, Buckner SA, Kuk J, Daza AV, Milicic IV, Cain JC, Kang CH, Ireland LM, Carr TL, Miller TR, Hancock AA, Nakane M, Esbenshade TA, Brune ME, O'Neill AB, Gauvin DM, Katwala SP, Holladay MW, Brioni JD, Sullivan JP: Synthesis and structure-activity studies on N-[5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenyl]methanesulfonamide, an imidazole-containing alpha(1A)-adrenoceptor agonist. J Med Chem. 2004 Jun 3;47(12):3220-35. [PubMed:15163201 ]

Details

2. Alpha-1B adrenergic receptor

Kind: Protein
Organism: Human
Pharmacological action: yes
Actions: agonist

General Function:: Protein heterodimerization activity
Specific Function:: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:: ADRA1B
Uniprot ID:: P35368
Molecular Weight:: 56835.375 Da

References

Altenbach RJ, Khilevich A, Kolasa T, Rohde JJ, Bhatia PA, Patel MV, Searle XB, Yang F, Bunnelle WH, Tietje K, Bayburt EK, Carroll WA, Meyer MD, Henry R, Buckner SA, Kuk J, Daza AV, Milicic IV, Cain JC, Kang CH, Ireland LM, Carr TL, Miller TR, Hancock AA, Nakane M, Esbenshade TA, Brune ME, O'Neill AB, Gauvin DM, Katwala SP, Holladay MW, Brioni JD, Sullivan JP: Synthesis and structure-activity studies on N-[5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenyl]methanesulfonamide, an imidazole-containing alpha(1A)-adrenoceptor agonist. J Med Chem. 2004 Jun 3;47(12):3220-35. [PubMed:15163201 ]

Details

3. Alpha-1D adrenergic receptor

Kind: Protein
Organism: Human
Pharmacological action: unknown
Actions: agonist

General Function:: Alpha1-adrenergic receptor activity
Specific Function:: This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:: ADRA1D
Uniprot ID:: P25100
Molecular Weight:: 60462.205 Da

References

Altenbach RJ, Khilevich A, Meyer MD, Buckner SA, Milicic I, Daza AV, Brune ME, O'Neill AB, Gauvin DM, Cain JC, Nakane M, Holladay MW, Williams M, Brioni JD, Sullivan JP: N-[3-(1H-imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1),(1) a novel alpha(1)-adrenoceptor ligand with an enhanced in vitro and in vivo profile relative to phenylpropanolamine and midodrine. J Med Chem. 2002 Sep 26;45(20):4395-7. [PubMed:12238918 ]

Enzymes

Details

1. Cytochrome P450 2D6

Kind: Protein
Organism: Human
Pharmacological action: unknown
Actions: inhibitor

General Function:: Steroid hydroxylase activity
Specific Function:: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:: CYP2D6
Uniprot ID:: P10635
Molecular Weight:: 55768.94 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Transporters

Details

1. Solute carrier family 15 member 1

Kind: Protein
Organism: Human
Pharmacological action: unknown

General Function:: Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function:: Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name:: SLC15A1
Uniprot ID:: P46059
Molecular Weight:: 78805.265 Da

References

Tsuda M, Terada T, Irie M, Katsura T, Niida A, Tomita K, Fujii N, Inui K: Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60. Epub 2006 Apr 5. [PubMed:16597710 ]

Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:46

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Structure for DB00211 (Midodrine)

Targets

References

References

References

Enzymes

References

Transporters

References