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Identification
Name Alprostadil
Accession Number DB00770 (APRD00785)
Type small molecule
Groups approved
Description

Alprostadil is produced endogenously and causes vasodilation by means of a direct effect on vascular and ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This results in increased pulmonary or systemic blood flow in infants. In infants, it is used for palliative, not definitive, therapy to temporarily maintain the patency of the ductus arteriosus until corrective or palliative surgery can be performed in neonates who have congenital heart defects and who depend upon the patent ductus for survival. In adults, it is used for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Alista
Alprostadil Prostoglandin E1
Alprox-TD
Befar
Caverject
Edex
Femprox
l-Prostaglandin E1
Muse
PGE1
Prink
Prostaglandin E1
Prostin VR
Prostin VR Pediatric
Topiglan
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Brand mixtures
Brand Name Ingredients
Caverject Sterile Powder - Kit 11.9mcg /Vial Alprostadil + Water
Caverject Sterile Powder - Kit 23.2mcg/Vial Alprostadil + Water
Categories
  • Vasodilator Agents
  • Platelet Aggregation Inhibitors
  • Fibrinolytic Agents
CAS number 745-65-3
Weight Average: 354.481
Monoisotopic: 354.240624198
Chemical Formula C20H34O5
InChI Key InChIKey=GMVPRGQOIOIIMI-DWKJAMRDSA-N
InChI
InChI=1S/C20H34O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h12-13,15-17,19,21,23H,2-11,14H2,1H3,(H,24,25)/b13-12+/t15-,16+,17+,19+/m0/s1
Plain Text
IUPAC Name
7-[(1R,2R,3R)-3-hydroxy-2-[(3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid
SMILES
CCCCC[C@H](O)C=C[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carboxylic Acids and Derivatives
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
  • Ketones
Pharmacology
Indication For palliative, not definitive, therapy to temporarily maintain the patency of the ductus arteriosus until corrective or palliative surgery can be performed in neonates who have congenital heart defects and who depend upon the patent ductus for survival. Also for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.
Pharmacodynamics Alprostadil (prostaglandin E1) is produced endogenously to relax vascular smooth muscle and cause vasodilation. In adult males, the vasodilatory effects of alprostadil on the cavernosal arteries and the trabecular smooth muscle of the corpora cavernosa result in rapid arteriolar inflow and expansion of the lacunar spaces within the corpora. As the expanded corporal sinusoids are compressed against the tunica albuginea, venous outflow through the subtunical vessels is impeded and penile rigidity develops. This is referred to as the corporal veno-occlusive mechanism. In infants, the vasodilatory effects of alprostadil increase pulmonary or systemic blood flow.
Mechanism of action Alprostadil causes vasodilation by means of a direct effect on vascular and ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This is because, as a form of prostaglandinE1 (PGE1) it has multiple effects on blood flow. This results in increased pulmonary or systemic blood flow in infants. In cyanotic congenital heart disease, alprostadil's actions result in an increased oxygen supply to the tissues. In infants with interrupted aortic arch or very severe aortic coarctation, alprostadil maintains distal aortic perfusion by permitting blood flow through the DA from the pulmonary artery to the aorta. In infants with aortic coarctation, alprostadil reduces aortic obstruction either by relaxing ductus tissue in the aortic wall or by increasing effective aortic diameter by dilating the DA. In infants with these aortic arch anomalies, systemic blood flow to the lower body is increased, improving tissue oxygen supply and renal perfusion. When administered by intracavernosal injection or as an intraurethral suppository, alprostadil acts locally to relax the trabecular smooth muscle of the corpora cavernosa and the cavernosal arteries. Swelling, elongation, and rigidity of the penis result when arterial blood rapidly flows into the corpus cavernosum to expand the lacunar spaces. The entrapped blood reduces the venous blood outflow as sinusoids compress against the tunica albuginea.
Absorption The absolute bioavailability of alprostadil has not been determined.
Volume of distribution Not Available
Protein binding Bound in plasma primarily to albumin (81% bound) and to a lesser extent alpha-globulin IV-4 fraction (55% bound).
Metabolism Alprostadil must be infused continuously because it is very rapidly metabolized. As much as 80% of the circulating alprostadil may be metabolized in one pass through the lungs, primarily by beta- and omega-oxidation.
Route of elimination Alprostadil must be infused continuously because it is very rapidly metabolized. As much as 80% of the circulating alprostadil may be metabolized in one pass through the lungs, primarily by β- and ω-oxidation. The metabolites are excreted primarily by the kidney, and excretion is essentially complete within 24 hours after administration.
Half life 5 to 10 minutes (after a single dose), in healthy adults and neonates.
Clearance Not Available
Toxicity Oral, mouse: LD50 = 186 mg/kg; Oral, rat: LD50 = 228 mg/kg. Apnea, bradycardia, pyrexia, hypotension, and flushing may be signs of drug overdosage.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Bedford laboratories div ben venue laboratories inc
  • Teva parenteral medicines inc
  • Pfizer inc
  • Pharmacia and upjohn co
  • Schwarz pharma ag
  • Vivus inc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Solution Intra-arterial
Suppository Urethral
Prices
Unit description Cost Unit
Alprostadil powder 5049.0 USD g
Edex Cartridge 6 Pack 40 mcg Kit Box 412.4 USD box
Caverject 6 40 mcg Solution Box 341.78 USD box
Edex 6 Pack 20 mcg Kit Box 301.0 USD box
Caverject 6 20 mcg Solution, 1 Box Contains 6 Vials Box 272.05 USD box
Prostin Vr 500 mcg/ml 266.72 USD ml
Edex Cartridge 6 Pack 10 mcg Kit Box 233.65 USD box
Edex Cartridge 2 Pack 40 mcg Kit Box 135.23 USD box
Edex 40 mcg cartridge kit 132.18 USD kit
Prostin vr 500 mcg/ml ampul 108.0 USD ml
Edex 2 Pack 20 mcg Kit Box 97.47 USD box
Edex 20 mcg cartridge kit 96.47 USD kit
Edex Cartridge 2 Pack 10 mcg Kit Box 77.22 USD box
Edex 10 mcg cartridge kit 74.88 USD kit
Alprostadil 500 mcg/ml vial 66.0 USD ml
Caverject Impulse 1 Box = 2 Blister Trays, 20 mcg 47.77 USD box
Caverject impulse 20 mcg kit 46.66 USD each
Caverject Impulse 1 Box = 2 Blister Trays, 10 mcg 37.51 USD box
Muse 1000 mcg Pellets 36.97 USD pellet
Caverject impulse 10 mcg kit 36.23 USD each
Muse 1000 mcg urethral suppository 35.54 USD suppository
Muse 500 mcg Pellets 34.23 USD pellet
Muse 500 mcg urethral suppository 32.92 USD suppository
Muse 250 mcg Pellets 31.99 USD pellet
Muse 250 mcg urethral suppository 30.76 USD suppository
Muse 125 mcg Pellets 30.56 USD pellet
Muse 125 mcg urethral suppository 29.39 USD suppository
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Patents
Country Patent Number Approved Expires (estimated)
United States 5886039 1996-03-23 2016-03-23
United States 5773020 1993-04-25 2010-04-25
Canada 1335346 1995-04-25 2012-04-25
Properties
State solid
Experimental Properties
Property Value Source
melting point 115-116 °C Not Available
water solubility 26.7 mg/L Not Available
logP 3.20 AVDEEF,A ET AL. (1995)
pKa 4.85 (at 25 °C) AVDEEF,A ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 7.88e-02 g/l ALOGPS
logP 3.04 ALOGPS
logP 3.59 ChemAxon
logS -3.6 ALOGPS
pKa (strongest acidic) 4.35 ChemAxon
pKa (strongest basic) -1.6 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 94.83 ChemAxon
rotatable bond count 13 ChemAxon
refractivity 98.32 ChemAxon
polarizability 41.88 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00180 Link_out
KEGG Compound C04741 Link_out
PubChem Compound 5280723 Link_out
PubChem Substance 46508029 Link_out
ChemSpider 131636 Link_out
ChEBI 15544 Link_out
ChEMBL 15544 Link_out
Therapeutic Targets Database DAP001490 Link_out
PharmGKB PA448334 Link_out
IUPHAR 1882 Link_out
Guide to Pharmacology 1882 Link_out
Drug Product Database 2241680 Link_out
RxList http://www.rxlist.com/cgi/generic/alprostadil.htm Link_out
Drugs.com http://www.drugs.com/cdi/alprostadil.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cav1073.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Alprostadil Link_out
ATC Codes
  • C01EA01
  • G04BE01
AHFS Codes
  • 24:12.92
PDB Entries Not Available
FDA label show (283 KB)
MSDS show (74.3 KB)
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Prostaglandin E2 receptor, EP2 subtype

Pharmacological action: yes
Actions: agonist

Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle

Organism class: human
UniProt ID: P43116 Link_out
Gene: PTGER2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dijkstra BG, Schneemann A, Hoyng PF: Flow after prostaglandin E1 is mediated by receptor-coupled adenylyl cyclase in human anterior segments. Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2622-6. Pubmed
  2. Takahashi HK, Iwagaki H, Tamura R, Katsuno G, Xue D, Sugita S, Mori S, Yoshino T, Tanaka N, Nishibori M: Differential effect of prostaglandins E1 and E2 on lipopolysaccharide-induced adhesion molecule expression on human monocytes. Eur J Pharmacol. 2005 Apr 11;512(2-3):223-30. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostaglandin E2 receptor, EP1 subtype

Pharmacological action: yes
Actions: agonist

Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important modulator of renal function. Implicated the smooth muscle contractile response to PGE2 in various tissues

Organism class: human
UniProt ID: P34995 Link_out
Gene: PTGER1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Norel X, de Montpreville V, Brink C: Vasoconstriction induced by activation of EP1 and EP3 receptors in human lung: effects of ONO-AE-248, ONO-DI-004, ONO-8711 or ONO-8713. Prostaglandins Other Lipid Mediat. 2004 Oct;74(1-4):101-12. Pubmed
  2. Takahashi HK, Iwagaki H, Tamura R, Xue D, Sano M, Mori S, Yoshino T, Tanaka N, Nishibori M: Unique regulation profile of prostaglandin e1 on adhesion molecule expression and cytokine production in human peripheral blood mononuclear cells. J Pharmacol Exp Ther. 2003 Dec;307(3):1188-95. Epub 2003 Oct 15. Pubmed
  3. Ito Y, Murai Y, Ishibashi H, Onoue H, Akaike N: The prostaglandin E series modulates high-voltage-activated calcium channels probably through the EP3 receptor in rat paratracheal ganglia. Neuropharmacology. 2000 Jan 4;39(2):181-90. Pubmed
  4. Matlhagela K, Taub M: Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells. Prostaglandins Other Lipid Mediat. 2006 Mar;79(1-2):101-13. Epub 2006 Jan 27. Pubmed
  5. Tokuda H, Kozawa O, Miwa M, Uematsu T: p38 mitogen-activated protein (MAP) kinase but not p44/p42 MAP kinase is involved in prostaglandin E1-induced vascular endothelial growth factor synthesis in osteoblasts. J Endocrinol. 2001 Sep;170(3):629-38. Pubmed
Transporters

1. Multidrug resistance-associated protein 5

Actions: inhibitor

Acts as a multispecific organic anion pump which can transport nucleotide analogs

UniProt ID: O15440 Link_out
Gene: ABCC5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

2. Solute carrier organic anion transporter family member 2B1

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost

UniProt ID: O94956 Link_out
Gene: SLCO2B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nishio T, Adachi H, Nakagomi R, Tokui T, Sato E, Tanemoto M, Fujiwara K, Okabe M, Onogawa T, Suzuki T, Nakai D, Shiiba K, Suzuki M, Ohtani H, Kondo Y, Unno M, Ito S, Iinuma K, Nunoki K, Matsuno S, Abe T: Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate. Biochem Biophys Res Commun. 2000 Sep 7;275(3):831-8. Pubmed

3. Solute carrier organic anion transporter family member 3A1

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as estrone-3-sulfate (PubMed:10873595). Mediates transport of prostaglandins (PG) E1 and E2, thyroxine (T4), deltorphin II, BQ-123 and vasopressin, but not DPDPE (a derivative of enkephalin lacking an N-terminal tyrosine residue), estrone-3- sulfate, taurocholate, digoxin nor DHEAS (PubMed:16971491)

UniProt ID: Q9UIG8 Link_out
Gene: SLCO3A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T: Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97. Pubmed
  2. Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T: Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97. Pubmed

4. Multidrug resistance-associated protein 4

Actions: substrate

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

5. Solute carrier organic anion transporter family member 2A1

Actions: substrate

May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A

UniProt ID: Q92959 Link_out
Gene: SLCO2A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lu R, Kanai N, Bao Y, Schuster VL: Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9. Pubmed
  2. Kanai N, Lu R, Satriano JA, Bao Y, Wolkoff AW, Schuster VL: Identification and characterization of a prostaglandin transporter. Science. 1995 May 12;268(5212):866-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19