MIDODRINE

First approved in 1996

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H18N2O4
Molecular Weight	254.2823
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=PTKSEFOSCHHMPD-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00211
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/midodrine.html

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. 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. Midodrine is used for the treatment of symptomatic orthostatic hypotension (OH). Midodrine is marketed under the brand names Amatine, ProAmatine, Gutron.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-1a adrenergic receptor 66 Target ID: CHEMBL229 Sources: http://www.drugbank.ca/drugs/DB00211	Agonist 2678
Alpha-1b adrenergic receptor 44 Target ID: CHEMBL232 Sources: http://www.drugbank.ca/drugs/DB00211	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Orthostatic hypotension 4 Sources: https://www.drugs.com/pro/midodrine.html	Primary		Approved 8429	ORVATEN Approved Use indicated for the treatment of symptomatic orthostatic hypotension Launch Date 2004

C_max

Value	Dose	Co-administered	Analyte	Population
21 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26597181	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDODRINE HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26597181	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDODRINE HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
18.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26597181	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDODRINE HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26597181	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDODRINE HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.54 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26597181	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDODRINE HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26597181	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDODRINE HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
100% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26597181	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDODRINE HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
350 mg single, oral Overdose Dose: 350 mg Route: oral Route: single Dose: 350 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27417951	unhealthy, 20 years n = 1 Health Status: unhealthy Age Group: 20 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27417951	Other AEs: Hypertension, Bradycardia... Other AEs: Hypertension (severe, 1 patient) Bradycardia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/27417951
90 mg 1 times / day steady, oral Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: steady Dose: 90 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31381098	unhealthy, 49 years n = 1 Health Status: unhealthy Condition: hypotension Age Group: 49 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/31381098	Sources: https://pubmed.ncbi.nlm.nih.gov/31381098
2.5 mg single, intravenous Dose: 2.5 mg Route: intravenous Route: single Dose: 2.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7690382	healthy, adult n = 12 Health Status: healthy Age Group: adult Sex: M Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/7690382	Sources: https://pubmed.ncbi.nlm.nih.gov/7690382
205 mg single, oral Overdose Dose: 205 mg Route: oral Route: single Dose: 205 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf	unknown n = 1 Health Status: unknown Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf	Other AEs: Lethargic... Other AEs: Lethargic (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf
250 mg single, oral Overdose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf	unknown n = 1 Health Status: unknown Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf	Other AEs: Blood pressure systolic increased... Other AEs: Blood pressure systolic increased (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf
10 mg 3 times / day steady, oral Recommended Dose: 10 mg, 3 times / day Route: oral Route: steady Dose: 10 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf	unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf	Disc. AE: Supine hypertension... AEs leading to discontinuation/dose reduction: Supine hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf
7.5 mg 1 times / day steady, oral Dose: 7.5 mg, 1 times / day Route: oral Route: steady Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11007859	unhealthy n = 2 Health Status: unhealthy Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/11007859	Other AEs: Pancytopenia... Other AEs: Pancytopenia (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/11007859

AEs

AE	Significance	Dose	Population
Bradycardia	1 patient	350 mg single, oral Overdose Dose: 350 mg Route: oral Route: single Dose: 350 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27417951	unhealthy, 20 years n = 1 Health Status: unhealthy Age Group: 20 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27417951
Hypertension	severe, 1 patient	350 mg single, oral Overdose Dose: 350 mg Route: oral Route: single Dose: 350 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27417951	unhealthy, 20 years n = 1 Health Status: unhealthy Age Group: 20 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27417951
Lethargic	1 patient	205 mg single, oral Overdose Dose: 205 mg Route: oral Route: single Dose: 205 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf	unknown n = 1 Health Status: unknown Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf
Blood pressure systolic increased	1 patient	250 mg single, oral Overdose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf	unknown n = 1 Health Status: unknown Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf
Supine hypertension	Disc. AE	10 mg 3 times / day steady, oral Recommended Dose: 10 mg, 3 times / day Route: oral Route: steady Dose: 10 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf	unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019815s010lbl.pdf
Pancytopenia	2 patients	7.5 mg 1 times / day steady, oral Dose: 7.5 mg, 1 times / day Route: oral Route: steady Dose: 7.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11007859	unhealthy n = 2 Health Status: unhealthy Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/11007859

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6933	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6933
ChemicalBook	CB4297224	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4297224
MolPort	MolPort-003-849-221	https://www.molport.com/shop/molecule-link/MolPort-003-849-221

PubMed

Title	Date	PubMed
Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa.	2000 Dec	11145175
Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management.	2001	11482743
Syncope in pharmacologically unmasked Brugada syndrome: indication for an implantable defibrillator or an unresolved dilemma?	2001 Apr	11333057
Usefulness of midodrine in patients with severely symptomatic neurocardiogenic syncope: a randomized control study.	2001 Aug	11513446
[Pharmacologic stimulation of ejaculation with midodrine hydrochloride (Gutron) for medically assisted reproduction in spinal injury].	2001 Dec	11859662
Treatment of Severe Intradialytic Hypotension With the Addition of High Dialysate Calcium Concentration to Midodrine and/or Cool Dialysate.	2001 Feb	11157369
Midodrine prevents orthostatic intolerance associated with simulated spaceflight.	2001 Jun	11356789
Midodrine for the management of orthostatic hypotension in patients with spinal cord injury: A case report.	2001 May	11346851
Acarbose improved severe postprandial hypotension in a patient with diabetes mellitus.	2001 May-Jun	11358685
Computer systems analysis of the cardiovascular mechanisms of reentry orthostasis in astronauts.	2002	14686452
Strategy for the management of vasovagal syncope.	2002	12027777
Treatment of orthostatic hypotension.	2002 Dec	12482740
[Syncope - a systematic overview of classification, pathogenesis, diagnosis and management].	2002 Feb	11823926
Chronic hypotension in the dialysis patient.	2002 Jul-Aug	12243360
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.	2002 Sep 26	12238918
A pilot randomized trial of induced blood pressure elevation: effects on function and focal perfusion in acute and subacute stroke.	2003	12865611
Neurocardiogenic syncope in children : current concepts in diagnosis and management.	2003	12716219
[Blood pressure disorders during idiopathic Parkinson's disease].	2003 Aug 9	14506467
Efficacy and safety of midodrine in the treatment of dialysis-associated hypotension.	2003 Jan	12904123
Drug treatment of orthostatic hypotension and vasovagal syncope.	2003 Jan-Feb	12549988
Hepatorenal syndrome.	2003 Jan-Mar	15094702
Randomized clinical trials of neurally mediated syncope.	2003 Sep	12950522
Double-blinded, placebo-controlled trial of midodrine for exercise performance enhancement in tetraplegia: a pilot study.	2004	15478524
Dysautonomia in chronic fatigue syndrome: facts, hypotheses, implications.	2004	14962627
Reconsidering hepatorenal syndrome. Throw in the towel? Not so fast!	2004 Dec	15620124
Chiral investigation of midodrine, a long-acting alpha-adrenergic stimulating agent.	2004 Jul	15190580
Taste and smell disturbance with the alpha-adrenoceptor agonist midodrine.	2004 Nov	15466905
Effects of midodrine on exercise-induced hypotension and blood pressure recovery in autonomic failure.	2004 Nov	15273244
Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review.	2004 Oct	15280522
A patient responding to combined therapy with pirmenol and midodrine for refractory neurally mediated syncope complicated by prostatic hypertrophy.	2004 Sep	15717144
New approaches to the treatment and prevention of neurally mediated reflex (neurocardiogenic) syncope.	2004 Sep	15306096
Effects of therapy based on tilt testing results on the long-term outcome in patients with syncope.	2005 Jul	16136424
Adrenergic drugs for urinary incontinence in adults.	2005 Jul 20	16034867
Consequences of cardiovascular adaptation to spaceflight: implications for the use of pharmacological countermeasures.	2005 Jun	16038093
[Diabetes mellitus and orthostatic intolerance].	2005 Jun	15999765
Pregnancy in postural orthostatic tachycardia syndrome.	2005 Jun	15955196
Successful treatment of hypotension associated with stunned myocardium with oral midodrine therapy.	2005 Mar	15821841
Effect of mineralocorticoids on interdialytic weight gain in hemodialysis patients with perdialytic hypotension.	2005 Oct	16219052
[Pharmacotherapy of stress incontinence].	2005 Oct 14	16231235
Heat-related morbidity in patients with orthostatic hypotension and primary autonomic failure.	2005 Sep	15954131

Patents

Sample Use Guides

In Vivo Use Guide

10 mg orally three times a day. Do not give more frequently than every 3 hours, after the evening meal, or less than 4 hours before bedtime.

Route of Administration: Oral

In Vitro Use Guide

A decrease in atrial rate was elicited by high concentrations (above 10(-4) to 10(-3) M) of the sympathomimetic agent midodrine in guinea-pig right atrial preparation

Name

Type

Language

MIDODRINE

Official Name

English

Midodrine [WHO-DD]

Common Name

English

MIDODRINE [VANDF]

Common Name

English

ACETAMIDE, 2-AMINO-N-(2-(2,5-DIMETHOXYPHENYL)-2-HYDROXYETHYL)-, (±)-

Systematic Name

English

ST 1085

Code

English

(±)-2-AMINO-N-(.BETA.-HYDROXY-2,5-DIMETHOXYPHENETHYL)ACETAMIDE

Systematic Name

English

midodrine [INN]

Common Name

English

MIDODRINE [MI]

Common Name

English

MIDODRINE [HSDB]

Common Name

English

ST-1085

Code

English

Classification Tree Code System Code

NDF-RT

N0000175552