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 66 Target ID: CHEMBL229 Sources: http://www.drugbank.ca/drugs/DB00211	Agonist 2662
Alpha-1b adrenergic receptor 44 Target ID: CHEMBL232 Sources: http://www.drugbank.ca/drugs/DB00211	Agonist 2662

Conditions

Condition	Modality	Targets	Highest Phase	Product
Orthostatic hypotension 4 Sources: https://www.drugs.com/pro/midodrine.html	Primary		Approved 8360	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
Acute dystonia induced by adding midodrine, a selective alpha 1 agonist, to risperidone in a patient with catatonic schizophrenia.	2000 Spring	11001613
Treatment of Severe Intradialytic Hypotension With the Addition of High Dialysate Calcium Concentration to Midodrine and/or Cool Dialysate.	2001 Feb	11157369
Midodrine for the management of orthostatic hypotension in patients with spinal cord injury: A case report.	2001 May	11346851
Clinical case-based approach to understanding intradialytic hypotension.	2001 Oct	11602459
[Lipothymia and syncope in adolescents].	2002 Dec	12388955
[Syncope - a systematic overview of classification, pathogenesis, diagnosis and management].	2002 Feb	11823926
Orthostatic hypotension.	2002 May	12180246
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
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
[Efficacy and safety of a herbal drug containing hawthorn berries and D-camphor in hypotension and orthostatic circulatory disorders/results of a retrospective epidemiologic cohort study].	2005	16149711
[Treatment of ejaculation disorders].	2005 Feb	15664683
Consequences of cardiovascular adaptation to spaceflight: implications for the use of pharmacological countermeasures.	2005 Jun	16038093
Beneficial haemodynamic and renal sodium handling effects of combined midodrine and octreotide treatment in a cirrhotic patient with large hepatic hydrothorax and mild ascites.	2005 Nov	16105868
Effect of mineralocorticoids on interdialytic weight gain in hemodialysis patients with perdialytic hypotension.	2005 Oct	16219052

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 `Thu Jul 06 23:00:35 UTC 2023` Edited by `admin` on `Thu Jul 06 23:00:35 UTC 2023`
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