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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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Midodrin
  • Midodrina [INN-Spanish]
  • Midodrine HCL
  • midodrine hydrochloride
  • Midodrinum [INN-Latin]
Brand names
  • ProAmatine
Brand name mixtures Not Available
Categories
  • Vasoconstrictor Agents
  • Sympathomimetics
  • Adrenergic alpha-Agonists
CAS number 133163-28-7
Weight Average: 254.2823
Monoisotopic: 254.126657074
Chemical Formula C12H18N2O4
InChI Key InChIKey=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)
Plain Text
IUPAC Name
2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]acetamide
SMILES
COC1=CC(C(O)CNC(=O)CN)=C(OC)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzyl Alcohols and Derivatives
  • Phenols and Derivatives
  • Ethers
  • Hydroquinones
  • Phenethylamines
  • Anisoles
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Phenols and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Hydroquinones
  • Phenethylamines
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Alcohols and Polyols
  • Phenyl Esters
Pharmacology
Indication For the treatment of symptomatic orthostatic hypotension (OH).
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.
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
Pharmacoeconomics
Manufacturers
  • Apotex inc etobicoke site
  • Impax pharmaceuticals
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Upsher smith laboratories inc
  • Shire development inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Proamatine 10 mg tablet 5.91 USD tablet
Midodrine hcl 10 mg tablet 4.93 USD tablet
Proamatine 5 mg tablet 3.08 USD tablet
Midodrine hcl 5 mg tablet 2.47 USD tablet
Proamatine 2.5 mg tablet 1.53 USD tablet
Midodrine hcl 2.5 mg tablet 1.23 USD tablet
Apo-Midodrine 5 mg Tablet 0.59 USD tablet
Apo-Midodrine 2.5 mg Tablet 0.35 USD tablet
Patents Not Available
Properties
State solid
Melting point 200 to 203°C
Experimental Properties
Property Value Source
water solubility Soluble PhysProp
logP -0.5 PhysProp
pKa 7.8 Various sources
Predicted Properties
Property Value Source
water solubility 4.45e+00 g/l ALOGPS
logP -0.49 ALOGPS
logP -0.95 ChemAxon Molconvert
logS -1.76 ALOGPS
pKa 15.26 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 93.81 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 66.22 ChemAxon Molconvert
polarizability 26.65 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Hebenstreit G: [Treatment of hypotension caused by psychopharmacological drugs (author’s transl)] Wien Med Wochenschr. 1981 Feb 28;131(4):109-12. Pubmed
External Links
Resource Link
KEGG Compound C07890 Link_out
PubChem Compound 4195 Link_out
PubChem Substance 46507373 Link_out
ChemSpider 4050 Link_out
ChEBI 6933 Link_out
ChEMBL 6933 Link_out
Therapeutic Targets Database DAP000229 Link_out
PharmGKB PA450498 Link_out
Drug Product Database 1934406 Link_out
RxList http://www.rxlist.com/cgi/generic3/midodrine.htm Link_out
Drugs.com http://www.drugs.com/cdi/midodrine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Midodrine Link_out
ATC Codes
  • C01CA17
AHFS Codes
  • 12:12.04
  • 12:12.00
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Alpha-1A adrenergic receptor

Pharmacological action: yes
Actions: agonist

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) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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]methanesulfonami de, an imidazole-containing alpha(1A)-adrenoceptor agonist. J Med Chem. 2004 Jun 3;47(12):3220-35. Pubmed

2. Alpha-1B adrenergic receptor

Pharmacological action: yes
Actions: agonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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]methanesulfonami de, an imidazole-containing alpha(1A)-adrenoceptor agonist. J Med Chem. 2004 Jun 3;47(12):3220-35. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: inhibitor

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:02

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.