Spirapril
Identification
- Generic Name
- Spirapril
- DrugBank Accession Number
- DB01348
- Background
Spirapril is an ACE inhibitor antihypertensive drug used to treat hypertension. Spirapril is converted to the active spiraprilat after administration. ACE inhibitors are used primarily in treatment of hypertension and congestive heart failure.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Spirapril (DB01348)
- Weight
- Average: 466.614
Monoisotopic: 466.15961346 - Chemical Formula
- C22H30N2O5S2
- Synonyms
- Espirapril
- Spirapril
- Spiraprilum
- External IDs
- Sch 33844
Pharmacology
- Indication
Spirapril is an ACE inhibitor class drug used to treat hypertension.
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Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Spirapril is an angiotensin-converting enzyme (ACE) inhibitor. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. By blocking ACE, spirapril decreases angiotensin II which is a vasoconstrictor and inducer of aldosterone. So by inhibiting the enzymes, aldosterone secreation is decreased (so less sodium is reabsorbed) and there is a decrease in vasoconstriction. Combined, this leades to a decrease in blood pressure.
- Mechanism of action
Spiraprilat, the active metabolite of spirapril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Spiraprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.
Target Actions Organism AAngiotensin-converting enzyme inhibitorHumans - Absorption
Bioavailability is 50% following oral administration.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic. Converted to spiraprilat following oral administration.
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
30 to 35 hours
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
Pathway Category Spirapril Action Pathway Drug action Spirapril Metabolism Pathway Drug metabolism - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcebutolol The risk or severity of hyperkalemia can be increased when Acebutolol is combined with Spirapril. Aceclofenac The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Spirapril. Acemetacin The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Spirapril. Acetylsalicylic acid The therapeutic efficacy of Spirapril can be decreased when used in combination with Acetylsalicylic acid. Agrostis gigantea pollen The risk or severity of adverse effects can be increased when Spirapril is combined with Agrostis gigantea pollen. Agrostis stolonifera pollen The risk or severity of adverse effects can be increased when Spirapril is combined with Agrostis stolonifera pollen. Alclofenac The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Alclofenac is combined with Spirapril. Aldesleukin Aldesleukin may increase the hypotensive activities of Spirapril. Alfentanil Alfentanil may decrease the antihypertensive activities of Spirapril. Alfuzosin Alfuzosin may increase the hypotensive activities of Spirapril. 
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- Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice).
- Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
- Limit salt intake. Salt may attenuate the antihypertensive effect.
Products
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Ingredient UNII CAS InChI Key Spirapril hydrochloride OCC25LM897 94841-17-5 CLDOLNORSLLQDI-OOAIBONUSA-N - International/Other Brands
- Renormax
Categories
- ATC Codes
- C09AA11 — Spirapril
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Dipeptides
- Alternative Parents
- N-acyl-L-alpha-amino acids / Alpha amino acid esters / Alpha amino acid amides / Pyrrolidine carboxylic acids / N-acylpyrrolidines / Fatty acid esters / Dithioketals / Aralkylamines / Dicarboxylic acids and derivatives / Benzene and substituted derivatives show 12 more
- Substituents
- 1,3-dithiolane / Alpha-amino acid amide / Alpha-amino acid ester / Alpha-amino acid or derivatives / Alpha-dipeptide / Amine / Amino acid / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound show 33 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 96U2K78I3V
- CAS number
- 83647-97-6
- InChI Key
- HRWCVUIFMSZDJS-SZMVWBNQSA-N
- InChI
- InChI=1S/C22H30N2O5S2/c1-3-29-21(28)17(10-9-16-7-5-4-6-8-16)23-15(2)19(25)24-14-22(30-11-12-31-22)13-18(24)20(26)27/h4-8,15,17-18,23H,3,9-14H2,1-2H3,(H,26,27)/t15-,17-,18-/m0/s1
- IUPAC Name
- (8S)-7-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
- SMILES
- CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2(C[C@H]1C(O)=O)SCCS2
References
- General References
- Hannedouche T, Ikeni A, Marques LP, Natov S, Dechaux M, Schmitt F, Lacour B, Grunfeld JP: Renal effects of angiotensin II in normotensive subjects on short-term cilazapril treatment. J Cardiovasc Pharmacol. 1992;19 Suppl 6:S25-7. [Article]
- Noble S, Sorkin EM: Spirapril. A preliminary review of its pharmacology and therapeutic efficacy in the treatment of hypertension. Drugs. 1995 May;49(5):750-66. [Article]
- Rosendorff C, Patton J, Radford HM, Kalliatakis B: Alpha-adrenergic and angiotensin II pressor sensitivity in hypertensive patients treated with an angiotensin-converting enzyme inhibitor. J Cardiovasc Pharmacol. 1992;19 Suppl 6:S105-9. [Article]
- Shohat J, Wittenberg C, Erman A, Rosenfeld J, Boner G: Acute and chronic effects of spirapril, alone or in combination with isradipine on kidney function and blood pressure in patients with reduced kidney function and hypertension. Scand J Urol Nephrol. 1999 Feb;33(1):57-62. [Article]
- External Links
- Human Metabolome Database
- HMDB0015438
- KEGG Drug
- D08529
- PubChem Compound
- 5311447
- PubChem Substance
- 46506126
- ChemSpider
- 4470933
- BindingDB
- 50017124
- 36908
- ChEBI
- 135756
- ChEMBL
- CHEMBL431
- ZINC
- ZINC000004217459
- Therapeutic Targets Database
- DAP000911
- PharmGKB
- PA164776913
- Wikipedia
- Spirapril
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment High Blood Pressure (Hypertension) 1 4 Recruiting Treatment Cardiovascular Disease (CVD) / Type 2 Diabetes Mellitus 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0293 mg/mL ALOGPS logP 1.79 ALOGPS logP 1.6 ChemAxon logS -4.2 ALOGPS pKa (Strongest Acidic) 3.62 ChemAxon pKa (Strongest Basic) 5.2 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 95.94 Å2 ChemAxon Rotatable Bond Count 10 ChemAxon Refractivity 121.94 m3·mol-1 ChemAxon Polarizability 48.74 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.5287 Blood Brain Barrier - 0.9614 Caco-2 permeable - 0.83 P-glycoprotein substrate Substrate 0.8223 P-glycoprotein inhibitor I Non-inhibitor 0.6938 P-glycoprotein inhibitor II Non-inhibitor 0.7426 Renal organic cation transporter Non-inhibitor 0.8836 CYP450 2C9 substrate Non-substrate 0.833 CYP450 2D6 substrate Non-substrate 0.8553 CYP450 3A4 substrate Non-substrate 0.5658 CYP450 1A2 substrate Non-inhibitor 0.8439 CYP450 2C9 inhibitor Non-inhibitor 0.7259 CYP450 2D6 inhibitor Non-inhibitor 0.8813 CYP450 2C19 inhibitor Non-inhibitor 0.5956 CYP450 3A4 inhibitor Inhibitor 0.5073 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6331 Ames test Non AMES toxic 0.8764 Carcinogenicity Non-carcinogens 0.908 Biodegradation Not ready biodegradable 0.9115 Rat acute toxicity 2.2396 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9961 hERG inhibition (predictor II) Non-inhibitor 0.5579
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent...
- Gene Name
- ACE
- Uniprot ID
- P12821
- Uniprot Name
- Angiotensin-converting enzyme
- Molecular Weight
- 149713.675 Da
References
- Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. [Article]
- Maul B, Krause W, Pankow K, Becker M, Gembardt F, Alenina N, Walther T, Bader M, Siems WE: Central angiotensin II controls alcohol consumption via its AT1 receptor. FASEB J. 2005 Sep;19(11):1474-81. [Article]
- Hermida RC, Ayala DE, Fontao MJ, Mojon A, Alonso I, Fernandez JR: Administration-time-dependent effects of spirapril on ambulatory blood pressure in uncomplicated essential hypertension. Chronobiol Int. 2010 May;27(3):560-74. doi: 10.3109/07420528.2010.485411. [Article]
- Arend U, Albrecht S, Meisel E, Schmidt J: [Influence of ACE inhibitor spirapril on left ventricular hypertrophy]. Fortschr Med Orig. 2002 Dec 5;120(4):147-50. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Peptide:proton symporter activity
- Specific Function
- Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
- Gene Name
- SLC15A2
- Uniprot ID
- Q16348
- Uniprot Name
- Solute carrier family 15 member 2
- Molecular Weight
- 81782.77 Da
References
- Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19. [Article]
Drug created on June 30, 2007 18:15 / Updated on June 12, 2020 16:51