DT-Web

DB00881 - Quinapril


Identification
Name Quinapril
Accession Number DB00881 (APRD00523)
Type small molecule
Description Quinapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to quinaprilat (quinapril diacid) following oral administration. Quinaprilat is a competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Quinapril may be used to treat essential hypertension and congestive heart failure.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 438.5161
Groups approved
Monoisotopic Weight 438.21547208
Pharmacology
Indication For the treatment of hypertension and as adjunct therapy in the treatment of congestive heart failure. May also be used to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.
Mechanism of action There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Quinaprilat, the principle active metabolite of quinapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Quinaprilat also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.
Absorption Peak plasma concentrations of quinapril occur within one hour following oral administration. The extent of absorption is at least 60%. The rate and extent of quinapril absorption are diminished moderately (approximately 25-30%) when ACCUPRIL tablets are administered during a high-fat meal.
Protein binding 97%
Biotransformation Hepatic.
Route of elimination Quinaprilat is eliminated primarily by renal excretion, up to 96% of an IV dose
Toxicity Overdose may lead to severe hypotension. LD50=1739mg/kg (orally in mice). The most common adverse effects observed in controlled clinical trials were dizziness, cough, chest pain, dyspnea, fatigue, and nausea/vomiting.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Amiloride Increased risk of hyperkalemia
Azilsartan medoxomil Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Drospirenone Increased risk of hyperkalemia
Icatibant Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Lithium The ACE inhibitor increases serum levels of lithium
Potassium Increased risk of hyperkalemia
Spironolactone Increased risk of hyperkalemia
Tetracycline Quinapril may decrease the absorption of tetracycline.
Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
Tobramycin Increased risk of nephrotoxicity
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Triamterene Increased risk of hyperkalemia
Trovafloxacin Quinapril may decrease the absorption of orally administered Trovafloxacin. The Quinapril formulation contains magnesium ions that may intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Quinapril dose to minimize the interaction.
Food Interactions
  • Do not take with a high-fat meal.
  • Herbs that may attenuate the antihypertensive effect of quinapril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
  • High salt intake may attenuate the antihypertensive effect of quinapril.
  • Quinapril may decrease the excretion of potassium. Salt substitutes containing potassium may increase the risk of hyperkalemia.

Targets


Angiotensin-converting enzyme
Name Angiotensin-converting enzyme
Gene Name ACE
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Culy CR, Jarvis B: Quinapril: a further update of its pharmacology and therapeutic use in cardiovascular disorders. Drugs. 2002;62(2):339-85. - Pubmed
  • Klutchko S, Blankley CJ, Fleming RW, Hinkley JM, Werner AE, Nordin I, Holmes A, Hoefle ML, Cohen DM, Essenburg AD, et al.: Synthesis of novel angiotensin converting enzyme inhibitor quinapril and related compounds. A divergence of structure-activity relationships for non-sulfhydryl and sulfhydryl types. J Med Chem. 1986 Oct;29(10):1953-61. - Pubmed
  • Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. - Pubmed
DTHybrid score 0.6488

Transporters


Oligopeptide transporter, small intestine isoform
Name Oligopeptide transporter, small intestine isoform
Gene Name SLC15A1
Actions substrate
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. Epub 2008 Aug 19. - Pubmed
DTHybrid score 0.6645
Oligopeptide transporter, kidney isoform
Name Oligopeptide transporter, kidney isoform
Gene Name SLC15A2
Actions substrate
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. Epub 2008 Aug 19. - Pubmed
DTHybrid score 0.6118

Predictions


Id Partner name Gene Name Score
633 Penicillin-binding proteins 1A/1B pbpA 0.1007
1385 Angiotensin-converting enzyme 2 ACE2 0.0956
1729 Solute carrier family 22 member 6 SLC22A6 0.082
118 Organic cation/carnitine transporter 2 SLC22A5 0.0813
1588 Multidrug resistance protein 1 ABCB1 0.0629
1 Peptidoglycan synthetase ftsI ftsI 0.0442
4155 Peptidoglycan synthetase ftsI ftsI 0.0442
294 Neprilysin MME 0.0432
3923 Cholinesterase BCHE 0.043
6142 Solute carrier family 22 member 8 SLC22A8 0.043
645 Penicillin-binding protein 1A mrcA 0.0413
5805 Penicillin-binding protein 1A ponA 0.0413
6185 Penicillin-binding protein 1A mrcA 0.0413
6799 Penicillin-binding protein 1A pbpA 0.0413
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0386
587 Serum albumin ALB 0.0369
471 Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) SLC6A14 0.036
3917 Methylenetetrahydrofolate reductase MTHFR 0.0347
4604 Liver carboxylesterase 1 CES1 0.0333
543 Penicillin-binding protein 1B mrcB 0.0309
6186 Penicillin-binding protein 1B ponB 0.0309
6822 Penicillin-binding protein 1b pbp1b 0.0309
6844 Penicillin-binding protein 1b pbp1b 0.0309
234 Plasminogen PLG 0.0246
1757 Myeloperoxidase MPO 0.0242
115 Penicillin-binding protein 2 mrdA 0.0235
6069 Penicillin-binding protein 2 mrdA 0.0235
6118 Penicillin-binding protein 2 penA 0.0235
6187 Penicillin-binding protein 2 pbpA 0.0235
6686 Penicillin-binding protein 2 pbp2 0.0235
6939 Penicillin-binding protein 2 mrdA 0.0235
7163 Penicillin-binding protein 2 pbpA 0.0235
6067 Penicillin binding protein 2a mecA 0.0233
56 Delta-aminolevulinic acid dehydratase ALAD 0.023
2356 Delta-aminolevulinic acid dehydratase hemB 0.023
3613 Delta-aminolevulinic acid dehydratase hemB 0.023
3674 Delta-aminolevulinic acid dehydratase hemB 0.023
6702 Organic hydroperoxide resistance protein, putative VC_A1006 0.0228
4587 Carbapenem-hydrolyzing beta-lactamase blaB-1 blaB1 0.0228
4586 FEZ-1 protein blaFEZ-1 0.0228
4512 Cytochrome P450 3A4 CYP3A4 0.0218
6143 Solute carrier family 22 member 7 SLC22A7 0.0203
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0203
2544 Bacterial leucyl aminopeptidase Not Available 0.0198
1024 Solute carrier family 22 member 11 SLC22A11 0.0197
6016 Cytochrome P450 2C19 CYP2C19 0.0172
4119 Cytochrome P450 2D6 CYP2D6 0.0172
707 72 kDa type IV collagenase MMP2 0.0167
3060 Leukotriene A-4 hydrolase LTA4H 0.0149
5754 Metallo-beta-lactamase L1 Not Available 0.0143
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.0142
3626 Probable polysaccharide deacetylase pdaA pdaA 0.0138
65 Matrix metalloproteinase-9 Not Available 0.0135
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.013
4787 Envelope glycoprotein gp160 env 0.0125
4820 Envelope glycoprotein gp160 env 0.0125
5727 Envelope glycoprotein gp160 env 0.0125
159 Penicillin-binding protein 2B penA 0.0123
6121 Penicillin-binding protein 2B penA 0.0123
4252 Penicillin-binding protein 5 dacA 0.0117
4757 Cytochrome P450 2C9 CYP2C9 0.0117
1373 Glucosylceramidase GBA 0.0114
4666 Fucose-binding lectin PA-IIL lecB 0.0114
738 Monocarboxylate transporter 1 SLC16A1 0.0104
3140 Hemagglutinin-neuraminidase HN 0.0104
3609 Hemagglutinin-neuraminidase HN 0.0104
332 Beta-lactamase blaZ 0.0102
2478 Beta-lactamase ampC 0.0102
2613 Beta-lactamase ampC 0.0102
2635 Beta-lactamase ampC 0.0102
2700 Beta-lactamase penP 0.0102
5445 Beta-lactamase blaB 0.0102
6019 Beta-lactamase SHV-7 0.0102
6701 Beta-lactamase cphA 0.0102
509 Thymidine kinase TK 0.0101
570 Thymidine kinase TK 0.0101
2559 Thymidine kinase TK 0.0101
3430 Thymidine kinase tdk 0.0101
3518 Thymidine kinase TK 0.0101
5301 Thymidine kinase tdk 0.0101
5771 Thymidine kinase ORF36 0.0101
7009 Thymidine kinase ORF36 0.0101
3810 Catechol O-methyltransferase COMT 0.0092
3760 Penicillin-binding protein 5 precursor dacA 0.0091
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0089
3426 Glutamine synthetase glnA 0.0089
3987 Glutamine synthetase GLUL 0.0089
6184 D-alanyl-D-alanine carboxypeptidase dacC dacC 0.0088
338 DNA polymerase UL30 0.0087
379 DNA polymerase UL54 0.0087
697 DNA polymerase ORF28 0.0087
2482 DNA polymerase 43 0.0087
4104 DNA polymerase BALF5 0.0087
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0084
867 Penicillin-binding protein 3 pbpC 0.0083
6119 Penicillin-binding protein 3 pbp3 0.0083
7154 Penicillin-binding protein 3 pbp3 0.0083
7157 Penicillin-binding protein 3 LMHCC_2184 0.0083
7162 Penicillin-binding protein 3 pbpB 0.0083
7172 Penicillin-binding protein 3 pbp3 0.0083
6113 MecA PBP2' (penicillin binding protein 2') mecA 0.0082
20 Prostaglandin G/H synthase 1 PTGS1 0.0078
4785 Ig gamma-1 chain C region IGHG1 0.0074
318 Alpha-2A adrenergic receptor ADRA2A 0.0071
1141 Sialidase-1 NEU1 0.0068
64 Neuraminidase NA 0.0068
641 Neuraminidase NA 0.0068
2676 Neuraminidase NA 0.0068
3026 Neuraminidase NA 0.0068
3519 Neuraminidase NA 0.0068
6007 Neuraminidase NA 0.0068
2164 Multidrug resistance-associated protein 4 ABCC4 0.0063
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.006
474 Acetylcholinesterase ACHE 0.006
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0059
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0059
632 Alpha-1B adrenergic receptor ADRA1B 0.0056
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0054
5482 Sialidase-2 NEU2 0.0052
556 Alpha-1A adrenergic receptor ADRA1A 0.005
6106 Cytochrome P450 2C18 CYP2C18 0.0048
833 Organic cation/carnitine transporter 1 SLC22A4 0.0048
2461 D-alanyl-D-alanine carboxypeptidase Not Available 0.0046
5756 D-alanyl-D-alanine carboxypeptidase dac 0.0046
3961 G protein-activated inward rectifier potassium channel 4 KCNJ5 0.0046
4924 Cytochrome P450 2C8 CYP2C8 0.0043
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0038
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0035
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0034
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0033
4118 Cytochrome P450 3A5 CYP3A5 0.0033
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0032
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0031
1181 Alpha-1-acid glycoprotein 1 ORM1 0.003
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.003
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0029
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0029
6107 Cytochrome P450 3A7 CYP3A7 0.0024
163 D(1B) dopamine receptor DRD5 0.0024
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0023
432 D(4) dopamine receptor DRD4 0.0023
638 D(3) dopamine receptor DRD3 0.0022
6151 Monocarboxylate transporter 10 SLC16A10 0.0022
776 Bile salt export pump ABCB11 0.0022
862 Multidrug resistance-associated protein 1 ABCC1 0.002
23 D(1A) dopamine receptor DRD1 0.002
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0019
831 D(2) dopamine receptor DRD2 0.0018
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0018
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0017
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0017
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0015
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0014
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0014
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0014
6024 Cytochrome P450 1A1 CYP1A1 0.0011
6030 Cytochrome P450 2B6 CYP2B6 0.0011
4200 Cytochrome P450 1A2 CYP1A2 0.0009
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