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Showing drug card for Midodrine (DB00211)

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Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:31
Primary Accession Number DB00211
Secondary Accession Number
  • APRD01116
Name Midodrine
Drug Type
  • Approved
  • Small Molecule
Description An ethanolamine derivative that is an adrenergic alpha agonist. It is used as a vasoconstrictor agent in the treatment of hypotension. [PubChem]
Synonyms
  1. Midodrin
  2. Midodrina [INN-Spanish]
  3. Midodrine HCL
  4. Midodrinum [INN-Latin]
  5. midodrine hydrochloride
Brand Names
  1. ProAmatine
Brand Mixtures Not Available
Chemical IUPAC Name 2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]acetamide
Chemical Formula C12H18N2O4
Chemical Structure Structure
CAS Registry Number 133163-28-7
InChI Identifier InChI=1/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)/f/h14H
InChI Key PTKSEFOSCHHMPD-YHMJCDSICD
KEGG Drug Not Available
KEGG Compound C07890 Link Image
PubChem Compound 4195 Link Image
PubChem Substance 10092 Link Image
ChEBI ID Not Available
PharmGKB ID PA450498 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 01934406 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/midodrine.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Midodrine Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 254.2823
Monoisotopic Molecular Weight 254.1267
State Solid
Melting Point 200 to 203°C
Experimental Water Solubility Soluble Source: PhysProp
Predicted Water Solubility 4.45e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -0.5 Source: PhysProp
Predicted LogP -0.49 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.76 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 7.8
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES COC1=CC([C@@H](O)CNC(=O)CN)=C(OC)C=C1
Canonical SMILES COC1=CC(C(O)CNC(=O)CN)=C(OC)C=C1
Drug Category
  • Adrenergic alpha-Agonists
  • Sympathomimetics
  • Vasoconstrictor Agents
ATC Codes
AHFS Codes
  • 12:12.00
  • 12:12.04
Indication For the treatment of symptomatic orthostatic hypotension (OH).
Pharmacology 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.
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.
Protein Binding Not Available
Biotransformation 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.
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.
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Betamethasone Increased arterial pressure
Cortisone acetate Increased arterial pressure
Dexamethasone Increased arterial pressure
Dobutamine Increased arterial pressure
Dopamine Increased arterial pressure
Ephedra Increased arterial pressure
Ephedrine Increased arterial pressure
Epinephrine Increased arterial pressure
Fenoterol Increased arterial pressure
Fludrocortisone Increased arterial pressure
Hydrocortisone Increased arterial pressure
Isocarboxazid Possible hypertensive crisis with this combination
Isoproterenol Increased arterial pressure
Mephentermine Increased arterial pressure
Metaraminol Increased arterial pressure
Methoxamine Increased arterial pressure
Methylprednisolone Increased arterial pressure
Norepinephrine Increased arterial pressure
Orciprenaline Increased arterial pressure
Paramethasone Increased arterial pressure
Phenelzine Possible hypertensive crisis with this combination
Phenylephrine Increased arterial pressure
Phenylpropanolamine Increased arterial pressure
Pirbuterol Increased arterial pressure
Prednisolone Increased arterial pressure
Prednisone Increased arterial pressure
Procaterol Increased arterial pressure
Pseudoephedrine Increased arterial pressure
Rasagiline Possible hypertensive crisis with this combination
Salbutamol Increased arterial pressure
Terbutaline Increased arterial pressure
Tranylcypromine Possible hypertensive crisis with this combination
Triamcinolone Increased arterial pressure
Food Interactions
  • Take without regard to meals.
Pathways Not Available
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 Link Image]
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Alpha-1A adrenergic receptor
  2. Alpha-1B adrenergic receptor
Drug Target 1 [top]
Target 1 ID 556
Target 1 Name Alpha-1A adrenergic receptor
Target 1 Synonyms
  1. Alpha 1A- adrenoreceptor
  2. Alpha 1A-adrenoceptor
  3. Alpha adrenergic receptor 1c
  4. Alpha-1C adrenergic receptor
Target 1 Gene Name ADRA1A
Target 1 Protein Sequence >Alpha-1A adrenergic receptor 
MVFLSGNASDSSNCTQPPAPVNISKAILLGVILGGLILFGVLGNILVILSVACHRHLHSV
THYYIVNLAVADLLLTSTVLPFSAIFEVLGYWAFGRVFCNIWAAVDVLCCTASIMGLCII
SIDRYIGVSYPLRYPTIVTQRRGLMALLCVWALSLVISIGPLFGWRQPAPEDETICQINE
EPGYVLFSALGSFYLPLAIILVMYCRVYVVAKRESRGLKSGLKTDKSDSEQVTLRIHRKN
APAGGSGMASAKTKTHFSVRLLKFSREKKAAKTLGIVVGCFVLCWLPFFLVMPIGSFFPD
FKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKKAFQNVLRIQCLCRKQSSKHALGYTL
HPPSQAVEGQHKDMVRIPVGSRETFYRISKTDGVCEWKFFSSMPRGSARITVSKDQSSCT
TARVRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV
Target 1 Number of Residues 473
Target 1 Molecular Weight 51487
Target 1 Theoretical pI 9.23
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
alpha-adrenergic receptor activity
alpha1-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in alpha1-adrenergic receptor activity
Target 1 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) proteins
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 28-51
  • 65-88
  • 100-122
  • 144-167
  • 182-205
  • 274-297
  • 306-329
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 433201 Link Image
Target 1 UniProtKB/Swiss-Prot ID P35348 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ADA1A_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1401 bp 
ATGGTGTTTCTCTCGGGAAATGCTTCCGACAGCTCCAACTGCACCCAACCGCCGGCACCG
GTGAACATTTCCAAGGCCATTCTGCTCGGGGTGATCTTGGGGGGCCTCATTCTTTTCGGG
GTGCTGGGTAACATCCTAGTGATCCTCTCCGTAGCCTGTCACCGACACCTGCACTCAGTC
ACGCACTACTACATCGTCAACCTGGCGGTGGCCGACCTCCTGCTCACCTCCACGGTGCTG
CCCTTCTCCGCCATCTTCGAGGTCCTAGGCTACTGGGCCTTCGGCAGGGTCTTCTGCAAC
ATCTGGGCGGCAGTGGATGTGCTGTGCTGCACCGCGTCCATCATGGGCCTCTGCATCATC
TCCATCGACCGCTACATCGGCGTGAGCTACCCGCTGCGCTACCCAACCATCGTCACCCAG
AGGAGGGGTCTCATGGCTCTGCTCTGCGTCTGGGCACTCTCCCTGGTCATATCCATTGGA
CCCCTGTTCGGCTGGAGGCAGCCGGCCCCCGAGGACGAGACCATCTGCCAGATCAACGAG
GAGCCGGGCTACGTGCTCTTCTCAGCGCTGGGCTCCTTCTACCTGCCTCTGGCCATCATC
CTGGTCATGTACTGCCGCGTCTACGTGGTGGCCAAGAGGGAGAGCCGGGGCCTCAAGTCT
GGCCTCAAGACCGACAAGTCGGACTCGGAGCAAGTGACGCTCCGCATCCATCGGAAAAAC
GCCCCGGCAGGAGGCAGCGGGATGGCCAGCGCCAAGACCAAGACGCACTTCTCAGTGAGG
CTCCTCAAGTTCTCCCGGGAGAAGAAAGCGGCCAAAACGCTGGGCATCGTGGTCGGCTGC
TTCGTCCTCTGCTGGCTGCCTTTTTTCTTAGTCATGCCCATTGGGTCTTTCTTCCCTGAT
TTCAAGCCCTCTGAAACAGTTTTTAAAATAGTATTTTGGCTCGGATATCTAAACAGCTGC
ATCAACCCCATCATATACCCATGCTCCAGCCAAGAGTTCAAAAAGGCCTTTCAGAATGTC
TTGAGAATCCAGTGTCTCCGCAGAAAGCAGTCTTCCAAACATGCCCTGGGCTACACCCTG
CACCCGCCCAGCCAGGCCGTGGAAGGGCAACACAAGGACATGGTGCGCATCCCCGTGGGA
TCAAGAGAGACCTTCTACAGGATCTCCAAGACGGATGGCGTTTGTGAATGGAAATTTTTC
TCTTCCATGCCCCGTGGATCTGCCAGGATTACAGTGTCCAAAGACCAATCCTCCTGTACC
ACAGCCCGGGTGAGAAGTAAAAGCTTTTTGGAGGTCTGCTGCTGTGTAGGGCCCTCAACC
CCCAGCCTTGACAAGAACCATCAAGTTCCAACCATTAAGGTCCACACCATCTCCCTCAGT
GAGAACGGGGAGGAAGTCTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID ADRA1A Link Image
Target 1 GenAtlas ID ADRA1A Link Image
Target 1 HGNC ID HGNC:277 Link Image
Target 1 Chromosome Location 8
Target 1 Locus 8p21-p11.2
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Hirasawa A, Shibata K, Horie K, Takei Y, Obika K, Tanaka T, Muramoto N, Takagaki K, Yano J, Tsujimoto G: Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants. FEBS Lett. 1995 Apr 24;363(3):256-60. [PubMed Link Image]
  2. Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ, et al.: Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther. 1995 Jan;272(1):134-42. [PubMed Link Image]
  3. Weinberg DH, Trivedi P, Tan CP, Mitra S, Perkins-Barrow A, Borkowski D, Strader CD, Bayne M: Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c. Biochem Biophys Res Commun. 1994 Jun 30;201(3):1296-304. [PubMed Link Image]
  4. Forray C, Bard JA, Wetzel JM, Chiu G, Shapiro E, Tang R, Lepor H, Hartig PR, Weinshank RL, Branchek TA, et al.: The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8. [PubMed Link Image]
  5. Hirasawa A, Horie K, Tanaka T, Takagaki K, Murai M, Yano J, Tsujimoto G: Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor. Biochem Biophys Res Commun. 1993 Sep 15;195(2):902-9. [PubMed Link Image]
  6. Tseng-Crank J, Kost T, Goetz A, Hazum S, Roberson KM, Haizlip J, Godinot N, Robertson CN, Saussy D: The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types. Br J Pharmacol. 1995 Aug;115(8):1475-85. [PubMed Link Image]
  7. Chang DJ, Chang TK, Yamanishi SS, Salazar FH, Kosaka AH, Khare R, Bhakta S, Jasper JR, Shieh IS, Lesnick JD, Ford AP, Daniels DV, Eglen RM, Clarke DE, Bach C, Chan HW: Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms. FEBS Lett. 1998 Jan 30;422(2):279-83. [PubMed Link Image]
Target 1 Drug 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 Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
Drug Target 2 [top]
Target 2 ID 632
Target 2 Name Alpha-1B adrenergic receptor
Target 2 Synonyms
  1. Alpha 1B- adrenoreceptor
  2. Alpha 1B-adrenoceptor
Target 2 Gene Name ADRA1B
Target 2 Protein Sequence >Alpha-1B adrenergic receptor 
MNPDLDTGHNTSAPAHWGELKNANFTGPNQTSSNSTLPQLDITRAISVGLVLGAFILFAI
VGNILVILSVACNRHLRTPTNYFIVNLAMADLLLSFTVLPFSAALEVLGYWVLGRIFCDI
WAAVDVLCCTASILSLCAISIDRYIGVRYSLQYPTLVTRRKAILALLSVWVLSTVISIGP
LLGWKEPAPNDDKECGVTEEPFYALFSSLGSFYIPLAVILVMYCRVYIVAKRTTKNLEAG
VMKEMSNSKELTLRIHSKNFHEDTLSSTKAKGHNPRSSIAVKLFKFSREKKAAKTLGIVV
GMFILCWLPFFIALPLGSLFSTLKPPDAVFKVVFWLGYFNSCLNPIIYPCSSKEFKRAFV
RILGCQCRGRGRRRRRRRRRLGGCAYTYRPWTRGGSLERSQSRKDSLDDSGSCLSGSQRT
LPSASPSPGYLGRGAPPPVELCAFPEWKAPGALLSLPAPEPPGRRGRHDSGPLFTFKLLT
EPESPGTDGGASNGGCEAAADVANGQPGFKSNMPLAPGQF
Target 2 Number of Residues 528
Target 2 Molecular Weight 56837
Target 2 Theoretical pI 9.79
Target 2 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
alpha-adrenergic receptor activity
alpha1-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in alpha1-adrenergic receptor activity
Target 2 Specific Function This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 46-70
  • 84-105
  • 116-141
  • 162-182
  • 202-224
  • 296-319
  • 327-340
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB/Swiss-Prot ID P35368 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name ADA1B_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence Not Available
Target 2 GenBank Gene ID
Target 2 GeneCard ID ADRA1B Link Image
Target 2 GenAtlas ID ADRA1B Link Image
Target 2 HGNC ID HGNC:278 Link Image
Target 2 Chromosome Location 5
Target 2 Locus 5q23-q32
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Ramarao CS, Denker JM, Perez DM, Gaivin RJ, Riek RP, Graham RM: Genomic organization and expression of the human alpha 1B-adrenergic receptor. J Biol Chem. 1992 Oct 25;267(30):21936-45. [PubMed Link Image]
  2. Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ, et al.: Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther. 1995 Jan;272(1):134-42. [PubMed Link Image]
  3. Forray C, Bard JA, Wetzel JM, Chiu G, Shapiro E, Tang R, Lepor H, Hartig PR, Weinshank RL, Branchek TA, et al.: The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8. [PubMed Link Image]
Target 2 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]

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.