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

Molecular Formula	C12H18N2O4
Molecular Weight	254.2823
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

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 64 Target ID: CHEMBL229 Sources: http://www.drugbank.ca/drugs/DB00211	Agonist 2637
Alpha-1b adrenergic receptor 42 Target ID: CHEMBL232 Sources: http://www.drugbank.ca/drugs/DB00211	Agonist 2637

Conditions

Condition	Modality	Targets	Highest Phase	Product
Orthostatic hypotension 4 Sources: https://www.drugs.com/pro/midodrine.html	Primary		Approved 8307	ORVATEN Approved Use indicated for the treatment of symptomatic orthostatic hypotension Launch Date 1.09935362E12

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
Diagnosis and treatment of diabetic autonomic neuropathy.	2001 Dec	12643202
[Pharmacologic stimulation of ejaculation with midodrine hydrochloride (Gutron) for medically assisted reproduction in spinal injury].	2001 Dec	11859662
Caudate hemorrhage as a possible complication of midodrine-induced supine hypertension.	2001 Dec	11761508
Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension.	2001 Sep	11511713
Drug treatment of orthostatic hypotension because of autonomic failure or neurocardiogenic syncope.	2002	14727996
Computer systems analysis of the cardiovascular mechanisms of reentry orthostasis in astronauts.	2002	14686452
[Vasoconstrictors in the treatment of hepatorenal syndrome].	2002	12107919
Strategy for the management of vasovagal syncope.	2002	12027777
Unusual causes of severe orthostatic hypotension.	2002 Apr	11995278
Pandysautonomia associated with impaired ganglionic neurotransmission and circulating antibody to the neuronal nicotinic receptor.	2002 Aug	12357282
ABT-866, a novel alpha(1A)-adrenoceptor agonist with antagonist properties at the alpha(1B)- and alpha(1D)-adrenoceptor subtypes.	2002 Aug 2	12163120
[Syncope - a systematic overview of classification, pathogenesis, diagnosis and management].	2002 Feb	11823926
Hemodynamics in patients with intradialytic hypotension treated with cool dialysate or midodrine.	2002 Jan	11774108
Chronic hypotension in the dialysis patient.	2002 Jul-Aug	12243360
Recurrent syncope in a 31-year-old army staff sergeant.	2002 Mar	11901579
Orthostatic hypotension.	2002 May	12180246
Supine hypertension during general anesthesia in a patient taking midodrine.	2002 Nov	12401592
Midodrine in neurally mediated syncope: a double-blind, randomized, crossover study.	2002 Sep	12205647
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
Adrenergic drugs for urinary incontinence in adults.	2003	12804414
Determination of midodrine in human plasma by high-performance liquid chromatography with fluorescence detection.	2003 Feb	12608767
Acute renal failure in patients with cirrhosis: perspectives in the age of MELD.	2003 Feb	12540770
Usefulness of intravenous metoprolol during positive isoproterenol tilt-table test in the choice of treatment for neurocardiogenic syncope.	2003 Jan-Feb	12760586
Drug treatment of orthostatic hypotension and vasovagal syncope.	2003 Jan-Feb	12549988
Hepatorenal syndrome.	2003 Jan-Mar	15094702
Successful treatment of chronic fatigue syndrome with midodrine: a pilot study.	2003 May-Jun	12846081
Effects of fatty acids and iontophoresis on the delivery of midodrine hydrochloride and the structure of human skin.	2003 Oct	14620516
Randomized clinical trials of neurally mediated syncope.	2003 Sep	12950522
[Successful midodrin treatment for vasovagal syncopes accompanied by asystole].	2004	15540425
[Results of midodrin treatment of vasovagal syncope].	2004	15471395
Dysautonomia in chronic fatigue syndrome: facts, hypotheses, implications.	2004	14962627
Postprandial hypotension treated with acarbose in a patient with type 1 diabetes mellitus.	2004 Dec	15666070
Reconsidering hepatorenal syndrome. Throw in the towel? Not so fast!	2004 Dec	15620124
Diabetic neuropathy: an intensive review.	2004 Jan 15	14750401
Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome.	2004 Jul	15239086
Chiral investigation of midodrine, a long-acting alpha-adrenergic stimulating agent.	2004 Jul	15190580
The in vitro metabolism of desglymidodrine, an active metabolite of prodrug midodrine by human liver microsomes.	2004 Jul-Sep	15537169
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.	2004 Jun 3	15163201
[Orthostatic hypotension and supine hypertension in pure autonomic failure].	2004 Nov	15633433
Management of vasovagal syncope: 2004.	2004 Nov	15500436
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
Fludrocortisone in patients with familial dysautonomia--assessing effect on clinical parameters and gene expression.	2005 Aug	16032383
[Pure autonomic failure. Bradbury Eggleston Syndrome. Case report].	2005 Feb	15824832
[Treatment of ejaculation disorders by midodrine (Gutron) per os. Retrospective study of about 16 subjects].	2005 Feb	15664682
Consequences of cardiovascular adaptation to spaceflight: implications for the use of pharmacological countermeasures.	2005 Jun	16038093
Pregnancy in postural orthostatic tachycardia syndrome.	2005 Jun	15955196
Successful treatment of hypotension associated with stunned myocardium with oral midodrine therapy.	2005 Mar	15821841
[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

Substance Class	Chemical Created by `admin` on `Sun Dec 18 20:37:08 UTC 2022` Edited by `admin` on `Sun Dec 18 20:37:08 UTC 2022`
Record UNII	6YE7PBM15H
Record Status	`Validated (UNII)`
Record Version

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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