Midodrine

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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.

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Midodrine (DB00211)

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Synonyms

• (±)-2-amino-N-(β-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
• Midodrine
• Midodrinum

External IDs

ST 1085 / ST-1085

Product Ingredients

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

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Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Amatine	Tablet		Oral	Shire Pharma Canada Ulc	1992-12-31	2010-10-04
Amatine	Tablet		Oral	Shire Pharma Canada Ulc	1992-12-31	2010-09-30
ProAmatine	Tablet	5 mg/1	Oral	Shire	1996-09-06	2010-12-31
ProAmatine	Tablet	2.5 mg/1	Oral	Shire	1996-09-06	2010-12-31
ProAmatine	Tablet	5 mg/1	Oral	Physicians Total Care, Inc.	2005-09-30	Not applicable
ProAmatine	Tablet	10 mg/1	Oral	Shire	1996-09-06	2010-12-31

Additional Data Available

Application Number
Application Number
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Apo-midodrine	Tablet		Oral	Apotex Corporation	2006-06-13	Not applicable
Apo-midodrine	Tablet		Oral	Apotex Corporation	2006-06-13	Not applicable
Mar-midodrine	Tablet		Oral	Marcan Pharmaceuticals Inc	2018-08-03	Not applicable
Mar-midodrine	Tablet		Oral	Marcan Pharmaceuticals Inc	2018-08-03	Not applicable
Midodrine HCl	Tablet	2.5 mg/1	Oral	Cardinal Health	2010-05-11	2019-05-31
Midodrine HCl	Tablet	5 mg/1	Oral	Eon Labs, Inc.	2003-09-11	2021-09-30
Midodrine HCl	Tablet	5 mg/1	Oral	Mc Kesson	2003-09-11	Not applicable
Midodrine HCl	Tablet	2.5 mg/1	Oral	Eon Labs, Inc.	2003-09-11	2021-03-31
Midodrine HCl	Tablet	10 mg/1	Oral	Rebel Distributors	2002-07-02	Not applicable
Midodrine HCl	Tablet	5 mg/1	Oral	Cardinal Health	2004-11-03	Not applicable

Additional Data Available

Application Number
Application Number
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Product Code
Product Code
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Categories

• Adrenergic Agents
• Adrenergic Agonists
• Adrenergic alpha-1 Receptor Agonists
• Adrenergic alpha-Agonists
• Adrenergic and Dopaminergic Agents
• Agents producing tachycardia
• Agents that produce hypertension
• Alcohols
• Amines
• Amino Alcohols
• Autonomic Agents
• Bradycardia-Causing Agents
• Cardiac Stimulants Excl. Cardiac Glycosides
• Cardiac Therapy
• Cardiovascular Agents
• Cytochrome P-450 CYP2D6 Substrates
• Cytochrome P-450 Substrates
• Ethanolamines
• Neurotransmitter Agents
• Peripheral Nervous System Agents
• Sympathomimetics
• Vasoconstrictor Agents

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).

Associated Conditions

• 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. 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 undergoes metabolism to form its pharmacologically active metabolite, desglymidodrine. Desglymidodrine acts as an agonist at the alpha₁-adrenergic receptors expressed in the arteriolar and venous vasculature. Activation of alpha₁-adrenergic receptor signaling pathways lead to an increase in the vascular tone and elevation of blood pressure. Desglymidodrine is reported to have negligible effect on the cardiac beta-adrenergic receptors.

Target	Actions	Organism
AAlpha-1A adrenergic receptor	agonist	Humans
AAlpha-1B adrenergic receptor	agonist	Humans
UAlpha-1D adrenergic receptor	agonist	Humans

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Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available

Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Rapidly absorbed following oral administration. The peak plasma concentrations of the prodrug, desglymidodrine, is reached about half an hour following drug administration. The metabolites reach their peak plasma concentrations at about 1 to 2 hours following drug administration. The absolute bioavailability of midodrine (measured as desglymidodrine) is 93% and is not affected by food. As desglymidodrine displays poor diffusibility across the blood-brain barrier, it is expected to have minimal effects on the central nervous system.

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.

• Midodrine
  desglymidodrine

Route of elimination

Not Available

Half life

The metabolites display 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

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• All Drugs
• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental

Drug	Interaction
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1-benzylimidazole	The risk or severity of hypertension can be increased when Midodrine is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamine	The risk or severity of adverse effects can be increased when Midodrine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine	The risk or severity of adverse effects can be increased when Midodrine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine	The risk or severity of adverse effects can be increased when Midodrine is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,5-diiodothyropropionic acid	The risk or severity of adverse effects can be increased when Midodrine is combined with 3,5-diiodothyropropionic acid.
3,5-Diiodotyrosine	The risk or severity of adverse effects can be increased when Midodrine is combined with 3,5-Diiodotyrosine.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of adverse effects can be increased when Midodrine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine	The risk or severity of hypertension can be increased when Midodrine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine	The risk or severity of hypertension can be increased when Midodrine is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanine	The risk or severity of adverse effects can be increased when Midodrine is combined with 6-O-benzylguanine.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
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Evidence Level
Evidence Level
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Action
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Food Interactions

• Take with or without food. The absorption is unaffected by food.

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

1. Hebenstreit G: [Treatment of hypotension caused by psychopharmacological drugs (author's transl)]. Wien Med Wochenschr. 1981 Feb 28;131(4):109-12. [PubMed:6165144]
2. 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

Human Metabolome Database

HMDB0014356

KEGG Drug

D08220

KEGG Compound

C07890

PubChem Compound

4195

PubChem Substance

46507373

ChemSpider

4050

RxNav

6963

ChEBI

6933

ChEMBL

CHEMBL1201212

Therapeutic Targets Database

DAP000229

PharmGKB

PA164749381

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Midodrine

ATC Codes

C01CA17 — Midodrine

• C01CA — Adrenergic and dopaminergic agents
• C01C — CARDIAC STIMULANTS EXCL. CARDIAC GLYCOSIDES
• C01 — CARDIAC THERAPY
• C — CARDIOVASCULAR SYSTEM

AHFS Codes

• 12:12.04 — Alpha-adrenergic Agonists

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Autonomic Failure / Orthostatic Hypotension	1
1	Completed	Not Available	Healthy Volunteers	3
1	Enrolling by Invitation	Other	Autonomic Failure / Multiple System Atrophy (MSA) / Orthostatic Hypotension / Progressive autonomic failure	1
1	Recruiting	Basic Science	Autonomic Failure / Multiple System Atrophy (MSA) / Orthostatic Hypotension / Parkinson's Disease (PD) / Progressive autonomic failure	1
1	Recruiting	Treatment	Blood Pressures / Sepsis	1
1	Recruiting	Treatment	Hepatopulmonary Syndrome (HPS)	1
1, 2	Active Not Recruiting	Treatment	Chronic Orthostatic Intolerance / Tachycardia	1
2	Completed	Treatment	Acute Ischemic Stroke (AIS)	1
2	Completed	Treatment	Influenza A Virus Infection	1
2	Completed	Treatment	Liver Cirrhosis / Renal Failure	1
2	Completed	Treatment	Orthostatic Hypotension	1
2	Completed	Treatment	Orthostatic Hypotension / Spinal Cord Injuries (SCI)	2
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	Withdrawn	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
2, 3	Recruiting	Treatment	Autonomic Dysreflexia / Baroreceptor Integrity / Blood Pressures / Cerebral Blood Flow / Hypotension / Orthostatic Hypotension / Spinal Cord Injuries (SCI) / Sympathetic Integrity / Vagal Integrity / Venous Occlusion Plethysmography	1
2, 3	Recruiting	Treatment	Renal Impairment in Hepatorenal Syndrome	1
2, 3	Terminated	Treatment	Hepatorenal Syndrome / Liver Cirrhosis	1
3	Completed	Prevention	Postoperative Orthostatic Hypotension / Postoperative Orthostatic Intolerance	1
3	Completed	Treatment	Hypotension / Illness, Critical	1
3	Completed	Treatment	Spinal Cord Injuries (SCI)	1
3	Recruiting	Treatment	Shock, Septic	1
3	Terminated	Treatment	Shock, Septic	1
4	Active Not Recruiting	Treatment	Vasovagal Syncope	1
4	Completed	Not Available	Hypothermia / Mild Cognitive Impairment (MCI) / Quadriplegia	1
4	Completed	Health Services Research	Shock, Septic	1
4	Completed	Prevention	Gastrointestinal Bleeding / Hepatic Encephalopathy (HE) / Hyponatremia / Renal Failure / Sepsis	1
4	Completed	Treatment	Ascites / Liver Cirrhosis	1
4	Completed	Treatment	Neurogenic Orthostatic Hypotension	1
4	Completed	Treatment	Orthostatic Hypotension	3
4	Completed	Treatment	Symptomatic Orthostatic Hypotension	1
4	Enrolling by Invitation	Treatment	Intradialytic Hypotension	1
4	Not Yet Recruiting	Treatment	Acute Renal Failure (ARF) / Hepatorenal Syndrome / Liver Cirrhosis	1
4	Recruiting	Supportive Care	Hypothermia / Mild Cognitive Impairment (MCI) / Quadriplegia	1
4	Recruiting	Treatment	Orthostatic; Hypotension, Neurogenic	1
4	Terminated	Treatment	Orthostatic Hypotension	1
4	Withdrawn	Supportive Care	Hypotension / Sepsis / Shock, Septic	1
Not Available	Completed	Not Available	Orthostatic Intolerance	1
Not Available	Completed	Treatment	Acute Kidney Injury (AKI)	1
Not Available	Completed	Treatment	Liver Cirrhosis	1
Not Available	Completed	Treatment	Syncope	1
Not Available	Not Yet Recruiting	Treatment	Children, Only / Refractory Ascites	1
Not Available	Not Yet Recruiting	Treatment	Cirrhosis, Decompensated / Severe Ascites	1
Not Available	Recruiting	Treatment	Hepatic Hydrothorax	1
Not Available	Recruiting	Treatment	Orthostatic Intolerance / Parkinson's Disease (PD)	1
Not Available	Terminated	Treatment	Orthostatic Hypotension	1
Not Available	Withdrawn	Not Available	Stroke	1
Not Available	Withdrawn	Treatment	Ascites / End Stage Liver Diseases / Hypotension / 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
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	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Taxonomy

Description

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

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Methoxybenzenes

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)

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Drug created on June 13, 2005 07:24 / Updated on February 27, 2020 21:29