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
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Midodrine hydrochloride59JV96YTXV43218-56-0MGCQZNBCJBRZDT-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmatineTablet2.5 mgOralShire Pharma Canada Ulc1992-12-312010-09-30Canada
AmatineTablet5 mgOralShire Pharma Canada Ulc1992-12-312010-10-04Canada
MidodrineTablet2.5 mgOralAa Pharma Inc2006-06-13Not applicableCanada
MidodrineTablet5.0 mgOralAa Pharma Inc2006-06-13Not applicableCanada
ProAmatineTablet2.5 mg/1OralShire1996-09-06Not applicableUs
ProAmatineTablet5 mg/1OralPhysicians Total Care, Inc.2005-09-30Not applicableUs
ProAmatineTablet5 mg/1OralShire1996-09-06Not applicableUs
ProAmatineTablet10 mg/1OralShire2002-03-20Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Midodrine HClTablet5 mg/1OralAmerincan Health Packaging2010-05-11Not applicableUs
Midodrine HClTablet2.5 mg/1OralAmerincan Health Packaging2010-05-11Not applicableUs
Midodrine HClTablet5 mg/1OralCardinal Health2004-11-032017-05-05Us
Midodrine HClTablet10 mg/1OralEon Labs, Inc.2002-07-02Not applicableUs
Midodrine HClTablet5 mg/1OralCardinal Health2012-11-26Not applicableUs
Midodrine HClTablet2.5 mg/1OralEon Labs, Inc.2003-09-11Not applicableUs
Midodrine HClTablet10 mg/1OralRebel Distributors2002-07-02Not applicableUs00185 0149 01 nlmimage10 7608bb65
Midodrine HClTablet5 mg/1OralMc Kesson Packaging Services A Buisness Unit Of Mc Kesson Corporation2012-11-26Not applicableUs00185 0043 01 nlmimage10 7208b925
Midodrine HClTablet2.5 mg/1OralCardinal Health2010-05-11Not applicableUs
Midodrine HClTablet5 mg/1OralCardinal Health2004-11-03Not applicableUs00245 0212 11 nlmimage10 cf3be79f
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
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.

TargetActionsOrganism
AAlpha-1A adrenergic receptor
agonist
Human
AAlpha-1B adrenergic receptor
agonist
Human
UAlpha-1D adrenergic receptor
agonist
Human
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.

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
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypertensive activities of Midodrine.Experimental
AcebutololAcebutolol may increase the bradycardic activities of Midodrine.Approved
AcetyldigitoxinAcetyldigitoxin may increase the bradycardic activities of Midodrine.Approved
AcetyldigoxinAcetyldigoxin may increase the bradycardic activities of Midodrine.Experimental
AlfuzosinAlfuzosin may decrease the vasoconstricting activities of Midodrine.Approved, Investigational
AlprenololAlprenolol may increase the bradycardic activities of Midodrine.Approved, Withdrawn
AmineptineAmineptine may increase the vasopressor activities of Midodrine.Illicit, Withdrawn
AmitriptylineAmitriptyline may increase the vasopressor activities of Midodrine.Approved
AmoxapineAmoxapine may increase the vasopressor activities of Midodrine.Approved
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Midodrine.Approved, Illicit
ArotinololArotinolol may increase the bradycardic activities of Midodrine.Approved, Investigational
AtenololAtenolol may increase the bradycardic activities of Midodrine.Approved
AtomoxetineAtomoxetine may increase the hypertensive activities of Midodrine.Approved
BefunololBefunolol may increase the bradycardic activities of Midodrine.Experimental
BenmoxinBenmoxin may increase the hypertensive activities of Midodrine.Withdrawn
BenzphetamineThe risk or severity of adverse effects can be increased when Midodrine is combined with Benzphetamine.Approved, Illicit
Benzylpenicilloyl PolylysineMidodrine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetaxololBetaxolol may increase the bradycardic activities of Midodrine.Approved
BevantololBevantolol may increase the bradycardic activities of Midodrine.Approved
BisoprololBisoprolol may increase the bradycardic activities of Midodrine.Approved
BopindololBopindolol may increase the bradycardic activities of Midodrine.Approved
BrofaromineBrofaromine may increase the hypertensive activities of Midodrine.Experimental
BromocriptineBromocriptine may increase the hypertensive activities of Midodrine.Approved, Investigational
BucindololBucindolol may increase the bradycardic activities of Midodrine.Investigational
BufuralolBufuralol may increase the bradycardic activities of Midodrine.Experimental, Investigational
BunazosinBunazosin may decrease the vasoconstricting activities of Midodrine.Investigational
BupranololBupranolol may increase the bradycardic activities of Midodrine.Approved
CabergolineCabergoline may increase the hypertensive activities of Midodrine.Approved
CaroxazoneCaroxazone may increase the hypertensive activities of Midodrine.Withdrawn
CarteololCarteolol may increase the bradycardic activities of Midodrine.Approved
CarvedilolCarvedilol may increase the bradycardic activities of Midodrine.Approved, Investigational
CeliprololCeliprolol may increase the bradycardic activities of Midodrine.Approved, Investigational
ChlorphentermineThe risk or severity of adverse effects can be increased when Midodrine is combined with Chlorphentermine.Illicit, Withdrawn
ClenbuterolThe risk or severity of adverse effects can be increased when Midodrine is combined with Clenbuterol.Approved, Investigational, Vet Approved
ClomipramineClomipramine may increase the vasopressor activities of Midodrine.Approved, Vet Approved
CloranololCloranolol may increase the bradycardic activities of Midodrine.Experimental
CyclobenzaprineCyclobenzaprine may increase the vasopressor activities of Midodrine.Approved
CymarinCymarin may increase the bradycardic activities of Midodrine.Experimental
DesipramineDesipramine may increase the vasopressor activities of Midodrine.Approved
DeslanosideDeslanoside may increase the bradycardic activities of Midodrine.Approved
DesvenlafaxineDesvenlafaxine may increase the tachycardic activities of Midodrine.Approved
DibenzepinDibenzepin may increase the vasopressor activities of Midodrine.Experimental
DigitoxinDigitoxin may increase the bradycardic activities of Midodrine.Approved, Investigational
DigoxinDigoxin may increase the bradycardic activities of Midodrine.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may increase the bradycardic activities of Midodrine.Approved
DihydroergotamineDihydroergotamine may increase the hypertensive activities of Midodrine.Approved
DiltiazemDiltiazem may increase the bradycardic activities of Midodrine.Approved
DobutamineThe risk or severity of adverse effects can be increased when Midodrine is combined with Dobutamine.Approved
DopamineThe risk or severity of adverse effects can be increased when Midodrine is combined with Dopamine.Approved
DosulepinDosulepin may increase the vasopressor activities of Midodrine.Approved
DoxazosinDoxazosin may decrease the vasoconstricting activities of Midodrine.Approved
DoxepinDoxepin may increase the vasopressor activities of Midodrine.Approved
DoxofyllineThe risk or severity of adverse effects can be increased when Midodrine is combined with Doxofylline.Approved
DronabinolDronabinol may increase the tachycardic activities of Midodrine.Approved, Illicit
DroxidopaMidodrine may increase the hypertensive activities of Droxidopa.Approved, Investigational
DuloxetineDuloxetine may increase the tachycardic activities of Midodrine.Approved
EpanololEpanolol may increase the bradycardic activities of Midodrine.Experimental
EphedrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Ephedrine.Approved
EpinephrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Epinephrine.Approved, Vet Approved
Ergoloid mesylateErgoloid mesylate may increase the hypertensive activities of Midodrine.Approved
ErgonovineErgonovine may increase the hypertensive activities of Midodrine.Approved
ErgotamineErgotamine may increase the hypertensive activities of Midodrine.Approved
EsmirtazapineEsmirtazapine may increase the vasopressor activities of Midodrine.Investigational
EsmololEsmolol may increase the bradycardic activities of Midodrine.Approved
EtilefrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Etilefrine.Withdrawn
FenoterolThe risk or severity of adverse effects can be increased when Midodrine is combined with Fenoterol.Approved, Investigational
FenozoloneThe risk or severity of adverse effects can be increased when Midodrine is combined with Fenozolone.Experimental
FentanylThe serum concentration of Fentanyl can be decreased when it is combined with Midodrine.Approved, Illicit, Investigational, Vet Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Midodrine.Approved
FurazolidoneFurazolidone may increase the hypertensive activities of Midodrine.Approved, Investigational, Vet Approved
GitoformateGitoformate may increase the bradycardic activities of Midodrine.Experimental
HarmalineHarmaline may increase the hypertensive activities of Midodrine.Experimental
HyaluronidaseHyaluronidase may increase the vasoconstricting activities of Midodrine.Approved, Investigational
HydracarbazineHydracarbazine may increase the hypertensive activities of Midodrine.Experimental
HydroxyamphetamineThe risk or severity of adverse effects can be increased when Midodrine is combined with Hydroxyamphetamine.Approved
ImipramineImipramine may increase the vasopressor activities of Midodrine.Approved
IndenololIndenolol may increase the bradycardic activities of Midodrine.Withdrawn
IndoraminIndoramin may decrease the vasoconstricting activities of Midodrine.Withdrawn
IobenguaneThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Midodrine.Approved, Investigational
IprindoleIprindole may increase the vasopressor activities of Midodrine.Experimental
IproclozideIproclozide may increase the hypertensive activities of Midodrine.Withdrawn
IproniazidIproniazid may increase the hypertensive activities of Midodrine.Withdrawn
IsocarboxazidIsocarboxazid may increase the hypertensive activities of Midodrine.Approved
IsoprenalineThe risk or severity of adverse effects can be increased when Midodrine is combined with Isoprenaline.Approved
IsoxsuprineThe risk or severity of adverse effects can be increased when Midodrine is combined with Isoxsuprine.Approved, Withdrawn
LabetalolLabetalol may increase the bradycardic activities of Midodrine.Approved
Lanatoside CLanatoside C may increase the bradycardic activities of Midodrine.Experimental
LandiololLandiolol may increase the bradycardic activities of Midodrine.Investigational
LevobunololLevobunolol may increase the bradycardic activities of Midodrine.Approved
LevomilnacipranLevomilnacipran may increase the tachycardic activities of Midodrine.Approved
LinezolidLinezolid may increase the hypertensive activities of Midodrine.Approved, Investigational
LofepramineLofepramine may increase the vasopressor activities of Midodrine.Experimental
MebanazineMebanazine may increase the hypertensive activities of Midodrine.Withdrawn
MefenorexThe risk or severity of adverse effects can be increased when Midodrine is combined with Mefenorex.Experimental
MephentermineThe risk or severity of adverse effects can be increased when Midodrine is combined with Mephentermine.Approved
MepindololMepindolol may increase the bradycardic activities of Midodrine.Experimental
MetaraminolThe risk or severity of adverse effects can be increased when Midodrine is combined with Metaraminol.Approved, Investigational
MethamphetamineThe risk or severity of adverse effects can be increased when Midodrine is combined with Methamphetamine.Approved, Illicit
MethoxamineThe risk or severity of adverse effects can be increased when Midodrine is combined with Methoxamine.Approved, Investigational
Methylene blueMethylene blue may increase the hypertensive activities of Midodrine.Approved, Investigational
MethylergometrineMethylergometrine may increase the hypertensive activities of Midodrine.Approved
MetildigoxinMetildigoxin may increase the bradycardic activities of Midodrine.Experimental
MetipranololMetipranolol may increase the bradycardic activities of Midodrine.Approved
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Midodrine.Approved, Investigational
MilnacipranMilnacipran may increase the tachycardic activities of Midodrine.Approved
MinaprineMinaprine may increase the hypertensive activities of Midodrine.Approved
MirtazapineMirtazapine may increase the vasopressor activities of Midodrine.Approved
MoclobemideMoclobemide may increase the hypertensive activities of Midodrine.Approved
NabiloneNabilone may increase the tachycardic activities of Midodrine.Approved, Investigational
NadololNadolol may increase the bradycardic activities of Midodrine.Approved
NebivololNebivolol may increase the bradycardic activities of Midodrine.Approved, Investigational
NialamideNialamide may increase the hypertensive activities of Midodrine.Withdrawn
NorepinephrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Norepinephrine.Approved
NortriptylineNortriptyline may increase the vasopressor activities of Midodrine.Approved
NylidrinThe risk or severity of adverse effects can be increased when Midodrine is combined with Nylidrin.Approved
OctamoxinOctamoxin may increase the hypertensive activities of Midodrine.Withdrawn
OleandrinOleandrin may increase the bradycardic activities of Midodrine.Experimental, Investigational
OpipramolOpipramol may increase the vasopressor activities of Midodrine.Investigational
OrciprenalineThe risk or severity of adverse effects can be increased when Midodrine is combined with Orciprenaline.Approved
OuabainOuabain may increase the bradycardic activities of Midodrine.Approved
OxprenololOxprenolol may increase the bradycardic activities of Midodrine.Approved
OxymetazolineThe risk or severity of adverse effects can be increased when Midodrine is combined with Oxymetazoline.Approved
PargylinePargyline may increase the hypertensive activities of Midodrine.Approved
PenbutololPenbutolol may increase the bradycardic activities of Midodrine.Approved, Investigational
PeruvosidePeruvoside may increase the bradycardic activities of Midodrine.Experimental
PhenelzinePhenelzine may increase the hypertensive activities of Midodrine.Approved
PheniprazinePheniprazine may increase the hypertensive activities of Midodrine.Withdrawn
PhenmetrazineThe risk or severity of adverse effects can be increased when Midodrine is combined with Phenmetrazine.Approved, Illicit
PhenoxypropazinePhenoxypropazine may increase the hypertensive activities of Midodrine.Withdrawn
PhentermineThe risk or severity of adverse effects can be increased when Phentermine is combined with Midodrine.Approved, Illicit
PhenylephrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Phenylephrine.Approved
PhenylpropanolamineThe risk or severity of adverse effects can be increased when Phenylpropanolamine is combined with Midodrine.Approved, Vet Approved, Withdrawn
PindololPindolol may increase the bradycardic activities of Midodrine.Approved
PirlindolePirlindole may increase the hypertensive activities of Midodrine.Approved
PivhydrazinePivhydrazine may increase the hypertensive activities of Midodrine.Withdrawn
Platelet Activating FactorPlatelet Activating Factor may increase the bradycardic activities of Midodrine.Experimental
PractololPractolol may increase the bradycardic activities of Midodrine.Approved
PrazosinPrazosin may decrease the vasoconstricting activities of Midodrine.Approved
PrenalterolThe risk or severity of adverse effects can be increased when Midodrine is combined with Prenalterol.Experimental
ProcarbazineProcarbazine may increase the hypertensive activities of Midodrine.Approved
ProcaterolThe risk or severity of adverse effects can be increased when Midodrine is combined with Procaterol.Approved, Investigational
PropranololPropranolol may increase the bradycardic activities of Midodrine.Approved, Investigational
ProscillaridinProscillaridin may increase the bradycardic activities of Midodrine.Experimental
ProtriptylineProtriptyline may increase the vasopressor activities of Midodrine.Approved
PseudoephedrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Pseudoephedrine.Approved
RacepinephrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Racepinephrine.Approved
RasagilineRasagiline may increase the hypertensive activities of Midodrine.Approved
RitodrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Ritodrine.Approved, Investigational
SafrazineSafrazine may increase the hypertensive activities of Midodrine.Withdrawn
SelegilineSelegiline may increase the hypertensive activities of Midodrine.Approved, Investigational, Vet Approved
SilodosinSilodosin may decrease the vasoconstricting activities of Midodrine.Approved
SotalolSotalol may increase the bradycardic activities of Midodrine.Approved
SpironolactoneSpironolactone may decrease the vasoconstricting activities of Midodrine.Approved
SynephrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Synephrine.Experimental
TalinololTalinolol may increase the bradycardic activities of Midodrine.Investigational
TamsulosinTamsulosin may decrease the vasoconstricting activities of Midodrine.Approved, Investigational
Tedizolid PhosphateTedizolid Phosphate may increase the hypertensive activities of Midodrine.Approved
TerazosinTerazosin may decrease the vasoconstricting activities of Midodrine.Approved
TerbutalineThe risk or severity of adverse effects can be increased when Midodrine is combined with Terbutaline.Approved
TertatololTertatolol may increase the bradycardic activities of Midodrine.Experimental
TetryzolineThe risk or severity of adverse effects can be increased when Midodrine is combined with Tetryzoline.Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Midodrine.Approved, Withdrawn
TianeptineTianeptine may increase the vasopressor activities of Midodrine.Approved, Investigational
TimololTimolol may increase the bradycardic activities of Midodrine.Approved
ToloxatoneToloxatone may increase the hypertensive activities of Midodrine.Approved
TramazolineThe risk or severity of adverse effects can be increased when Midodrine is combined with Tramazoline.Investigational
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypertensive activities of Midodrine.Experimental
TranylcypromineTranylcypromine may increase the hypertensive activities of Midodrine.Approved
TretoquinolThe risk or severity of adverse effects can be increased when Midodrine is combined with Tretoquinol.Experimental
TrimazosinTrimazosin may decrease the vasoconstricting activities of Midodrine.Experimental
TrimipramineTrimipramine may increase the vasopressor activities of Midodrine.Approved
TyramineThe risk or severity of adverse effects can be increased when Midodrine is combined with Tyramine.Investigational, Nutraceutical
UrapidilUrapidil may decrease the vasoconstricting activities of Midodrine.Investigational
VenlafaxineVenlafaxine may increase the tachycardic activities of Midodrine.Approved
VerapamilVerapamil 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
  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
HMDB14356
KEGG Compound
C07890
PubChem Compound
4195
PubChem Substance
46507373
ChemSpider
4050
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
AHFS Codes
  • 12:12.04 — Alpha-adrenergic Agonists

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAutonomic Failure / Idiopathic orthostatic hypotension1
1CompletedNot AvailableHealthy Volunteers3
1RecruitingNot AvailableAutonomic Failure / Idiopathic orthostatic hypotension / Multiple System Atrophy (MSA) / Progressive autonomic failure1
1RecruitingBasic ScienceAutonomic Failure / Idiopathic orthostatic hypotension / Multiple System Atrophy (MSA) / Parkinson's Disease (PD) / Progressive autonomic failure1
1RecruitingTreatmentBlood Pressures / Sepsis1
1, 2Active Not RecruitingTreatmentChronic Orthostatic Intolerance / Tachycardia1
2CompletedTreatmentAcute Ischemic Stroke (AIS)1
2CompletedTreatmentLiver Cirrhosis / Renal Failure1
2CompletedTreatmentIdiopathic orthostatic hypotension / Spinal Cord Injuries (SCI)2
2CompletedTreatmentIdiopathic orthostatic hypotension1
2RecruitingTreatmentAutonomic Dysreflexia / Autonomic Integrity / Baroreceptor Integrity / Blood Pressures / Cerebral Blood Flow / Cognitive Function / Hypotensive / Spinal Cord Injuries (SCI) / Sympathetic Integrity / Vagal Integrity1
2RecruitingTreatmentFibrosis / Hepatorenal Syndrome / Renal Failure1
2, 3Active Not RecruitingTreatmentLiver Cirrhosis / Refractory/Recurrent Ascites1
2, 3CompletedTreatmentRefractory Ascites / Type 2 Hepatorenal Syndrome1
3CompletedPreventionPostoperative Orthostatic Hypotension / Postoperative Orthostatic Intolerance1
3RecruitingTreatmentArterial Hypotension / Critical Illness1
3RecruitingTreatmentShock, Septic1
3RecruitingTreatmentSpinal Cord Injuries (SCI)1
4CompletedNot AvailableHypothermia / Mild Cognitive Impairment (MCI) / Quadriplegia1
4CompletedPreventionGastrointestinal Bleedings / Hepatic Encephalopathy / Hyponatremias / Renal Failure / Sepsis1
4CompletedTreatmentAscites / Liver Cirrhosis1
4CompletedTreatmentSymptomatic Orthostatic Hypotension1
4CompletedTreatmentIdiopathic orthostatic hypotension3
4Enrolling by InvitationTreatmentIntradialytic Hypotension1
4RecruitingSupportive CareHypothermia / Mild Cognitive Impairment (MCI) / Quadriplegia1
4RecruitingTreatmentOrthostatic; Hypotension, Neurogenic1
4RecruitingTreatmentSyncope, Vasovagal1
4TerminatedTreatmentIdiopathic orthostatic hypotension1
4WithdrawnSupportive CareArterial Hypotension / Sepsis / Shock, Septic1
Not AvailableCompletedNot AvailableOrthostatic Intolerance1
Not AvailableCompletedTreatmentSyncope1
Not AvailableNot Yet RecruitingTreatmentArterial Hypotension / Autonomic Dysreflexia / Baroreceptor Integrity / Blood Pressures / Cerebral Blood Flow / Idiopathic orthostatic hypotension / Spinal Cord Injuries (SCI) / Sympathetic Integrity / Vagal Integrity / Venous Occlusion Plethysmography1
Not AvailableRecruitingTreatmentLiver Cirrhosis1
Not AvailableRecruitingTreatmentOrthostatic Intolerance / Parkinson's Disease (PD)1
Not AvailableTerminatedTreatmentIdiopathic orthostatic hypotension1
Not AvailableWithdrawnNot AvailableStrokes1
Not AvailableWithdrawnTreatmentArterial Hypotension / Ascites / End Stage Liver Diseases / Liver Cirrhosis1

Pharmacoeconomics

Manufacturers
  • Apotex inc etobicoke site
  • Impax pharmaceuticals
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Upsher smith laboratories inc
  • Shire development inc
Packagers
Dosage forms
FormRouteStrength
TabletOral5 mg
TabletOral2.5 mg
TabletOral5.0 mg
TabletOral10 mg/1
TabletOral2.5 mg/1
TabletOral5 mg/1
Prices
Unit descriptionCostUnit
Proamatine 10 mg tablet5.91USD tablet
Midodrine hcl 10 mg tablet4.93USD tablet
Proamatine 5 mg tablet3.08USD tablet
Midodrine hcl 5 mg tablet2.47USD tablet
Proamatine 2.5 mg tablet1.53USD tablet
Midodrine hcl 2.5 mg tablet1.23USD tablet
Apo-Midodrine 5 mg Tablet0.59USD tablet
Apo-Midodrine 2.5 mg Tablet0.35USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)200 to 203°CNot Available
water solubilitySolubleNot Available
logP-0.5Not Available
pKa7.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.45 mg/mLALOGPS
logP-0.49ALOGPS
logP-0.95ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)13.77ChemAxon
pKa (Strongest Basic)8.14ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area93.81 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity66.22 m3·mol-1ChemAxon
Polarizability26.65 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7686
Blood Brain Barrier-0.856
Caco-2 permeable-0.7382
P-glycoprotein substrateSubstrate0.784
P-glycoprotein inhibitor INon-inhibitor0.9781
P-glycoprotein inhibitor IINon-inhibitor0.9866
Renal organic cation transporterNon-inhibitor0.8896
CYP450 2C9 substrateNon-substrate0.8519
CYP450 2D6 substrateNon-substrate0.7593
CYP450 3A4 substrateNon-substrate0.5595
CYP450 1A2 substrateInhibitor0.8848
CYP450 2C9 inhibitorNon-inhibitor0.9385
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8993
CYP450 3A4 inhibitorNon-inhibitor0.867
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9316
Ames testNon AMES toxic0.774
CarcinogenicityNon-carcinogens0.8613
BiodegradationNot ready biodegradable0.9595
Rat acute toxicity2.3137 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9772
hERG inhibition (predictor II)Non-inhibitor0.8604
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot 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)

Targets

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) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. 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]
  2. 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]
  3. 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]
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) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. 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]
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
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. 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

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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. 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]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Transporters

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
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. 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 November 19, 2017 20:33