DT-Web

DB00542 - Benazepril


Identification
Name Benazepril
Accession Number DB00542 (APRD00063)
Type small molecule
Description Benazepril, brand name Lotensin, is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 424.4895
Groups approved
Monoisotopic Weight 424.199822016
Pharmacology
Indication For the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.
Mechanism of action Benazeprilat, the active metabolite of Benazepril, 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. Benazeprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.
Absorption Peak in plasma within 0.5-1.0 hours. The extent of absorption is at least 37% as determined by urinary recovery and is not significantly influenced by the presence of food in the GI tract.
Protein binding benazepril, 97%; benazeprilat, 95%
Biotransformation Cleavage of the ester group (primarily in the liver) converts benazepril to its active metabolite, benazeprilat. Benazepril and benazeprilat may be conjugated to glucuronic acid prior to urinary excretion.
Route of elimination Benazepril and benazeprilat are cleared predominantly by renal excretion in healthy subjects with normal renal function. Nonrenal (i.e., biliary) excretion accounts for approximately 11%-12% of benazeprilat excretion in healthy subjects.
Toxicity Most likely symptom of overdosage is severe hypotension. Most common adverse effects include headache, dizziness, fatigue, somnolence, postural dizziness, nausea, and cough.
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
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
Food Interactions
  • Benazepril may decrease the excretion of potassium. Salt um may increase the risk of hyperkalemia. substitutes containing potassi
  • Food slows absorption without decreasing the quantity absorbed.
  • Herbs that may attenuate the antihypertensive effect of benazepril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
  • High salt intake may attenuate the antihypertensive effect of benazepril.
  • Take without regard to meals.

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
  • 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 0.6755

Enzymes


Methylenetetrahydrofolate reductase
Name Methylenetetrahydrofolate reductase
Gene Name MTHFR
Actions substrate
References
  • Jiang S, Yu Y, Venners SA, Zhang Y, Xing H, Wang X, Xu X: Effects of MTHFR and MS gene polymorphisms on baseline blood pressure and Benazepril effectiveness in Chinese hypertensive patients. J Hum Hypertens. 2010 May 6. - Pubmed
  • Jiang S, Hsu YH, Niu T, Xu X, Xing H, Chen C, Wang X, Zhang Y, Peng S, Xu X: A common haplotype on methylenetetrahydrofolate reductase gene modifies the effect of angiotensin-converting enzyme inhibitor on blood pressure in essential hypertension patients--a family-based association study. Clin Exp Hypertens. 2005 Aug;27(6):509-21. - Pubmed
  • Jiang S, Hsu YH, Xu X, Xing H, Chen C, Niu T, Zhang Y, Peng S, Xu X: The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor. Thromb Res. 2004;113(6):361-9. - Pubmed
DTHybrid score 0.1724

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 0.6857
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 0.6338

Predictions


Id Partner name Gene Name Score
1729 Solute carrier family 22 member 6 SLC22A6 0.1025
633 Penicillin-binding proteins 1A/1B pbpA 0.1007
1385 Angiotensin-converting enzyme 2 ACE2 0.0956
118 Organic cation/carnitine transporter 2 SLC22A5 0.0813
1588 Multidrug resistance protein 1 ABCB1 0.0649
6142 Solute carrier family 22 member 8 SLC22A8 0.0456
1 Peptidoglycan synthetase ftsI ftsI 0.0442
4155 Peptidoglycan synthetase ftsI ftsI 0.0442
294 Neprilysin MME 0.0432
587 Serum albumin ALB 0.0431
3923 Cholinesterase BCHE 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 0.0413
471 Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) SLC6A14 0.036
5698 Riboflavin synthase alpha chain ribE 0.0336
4604 Liver carboxylesterase 1 CES1 0.0333
408 Riboflavin kinase RFK 0.031
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
809 Methionine synthase MTR 0.0307
2935 Methionine synthase metH 0.0307
6143 Solute carrier family 22 member 7 SLC22A7 0.0283
234 Plasminogen PLG 0.0246
1757 Myeloperoxidase MPO 0.0242
840 Methionine synthase reductase, mitochondrial MTRR 0.0238
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
1024 Solute carrier family 22 member 11 SLC22A11 0.0227
4512 Cytochrome P450 3A4 CYP3A4 0.0218
2164 Multidrug resistance-associated protein 4 ABCC4 0.0218
293 Gamma-glutamyl hydrolase GGH 0.0216
654 Flavin reductase BLVRB 0.0214
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0203
2544 Bacterial leucyl aminopeptidase Not Available 0.0198
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0189
1650 Heme carrier protein 1 SLC46A1 0.0182
718 Folate receptor gamma FOLR3 0.0178
804 Mitochondrial folate transporter/carrier SLC25A32 0.0178
299 Folate receptor beta FOLR2 0.0178
6016 Cytochrome P450 2C19 CYP2C19 0.0172
4119 Cytochrome P450 2D6 CYP2D6 0.0172
3426 Glutamine synthetase glnA 0.0168
3987 Glutamine synthetase GLUL 0.0168
707 72 kDa type IV collagenase MMP2 0.0167
3941 Amine oxidase [flavin-containing] A MAOA 0.0154
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0153
507 Cob(I)yrinic acid a,c-diamide adenosyltransferase, mitochondrial MMAB 0.0152
3916 Methylmalonic aciduria and homocystinuria type C protein MMACHC 0.0152
354 Methylmalonic aciduria type A protein, mitochondrial MMAA 0.0152
398 Transcobalamin-2 TCN2 0.0152
265 Transcobalamin-1 TCN1 0.0152
376 Amnionless protein AMN 0.0152
854 Methylmalonyl-CoA mutase, mitochondrial MUT 0.0152
1224 Cubilin CUBN 0.0152
4757 Cytochrome P450 2C9 CYP2C9 0.015
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0149
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
738 Monocarboxylate transporter 1 SLC16A1 0.0137
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
317 Methionine-R-sulfoxide reductase SEPX1 0.0123
480 Methionine-R-sulfoxide reductase B2 MSRB2 0.0122
3996 Betaine--homocysteine S-methyltransferase 2 BHMT2 0.0122
3921 Methionine adenosyltransferase 2 subunit beta MAT2B 0.0122
3995 Methionyl-tRNA synthetase, mitochondrial MARS2 0.0122
600 Methionyl-tRNA synthetase, cytoplasmic MARS 0.0122
3763 5,10-methylenetetrahydrofolate reductase metF 0.0122
3918 5,10-methylenetetrahydrofolate reductase MTHFR 0.0122
5094 5,10-methylenetetrahydrofolate reductase metF 0.0122
4252 Penicillin-binding protein 5 dacA 0.0117
3920 Methylenetetrahydrofolate reductase intermediate form MTHFR 0.0117
1373 Glucosylceramidase GBA 0.0114
4666 Fucose-binding lectin PA-IIL lecB 0.0114
2287 Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase ATIC 0.0111
4226 Uridine phosphorylase 2 UPP2 0.011
3919 Methionyl-tRNA formyltransferase, mitochondrial MTFMT 0.0109
1202 10-formyltetrahydrofolate dehydrogenase ALDH1L1 0.0109
59 AMT protein AMT 0.0109
400 Coagulation factor IX F9 0.0107
5461 Coagulation factor IX F9 0.0107
334 S-adenosylmethionine synthetase isoform type-2 MAT2A 0.0106
3140 Hemagglutinin-neuraminidase HN 0.0104
3609 Hemagglutinin-neuraminidase HN 0.0104
191 Peptide methionine sulfoxide reductase MSRA 0.0102
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
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0101
4081 Vitamin K epoxide reductase complex subunit 1-like protein 1 VKORC1L1 0.01
604 Vitamin K-dependent protein Z PROZ 0.01
453 S-adenosylmethionine synthetase isoform type-1 MAT1A 0.0095
6013 Cytochrome P450 2E1 CYP2E1 0.0095
941 Betaine--homocysteine S-methyltransferase 1 BHMT 0.0095
24 Thymidylate synthase TMP1 0.0094
359 Thymidylate synthase TYMS 0.0094
2626 Thymidylate synthase thyA 0.0094
2729 Thymidylate synthase thyA 0.0094
5352 Thymidylate synthase THYA 0.0094
6020 Aldehyde oxidase AOX1 0.0094
4225 Uridine phosphorylase 1 UPP1 0.0094
413 Amidophosphoribosyltransferase PPAT 0.0094
2515 Amidophosphoribosyltransferase purF 0.0094
3714 Amidophosphoribosyltransferase purF 0.0094
3810 Catechol O-methyltransferase COMT 0.0092
3760 Penicillin-binding protein 5 precursor dacA 0.0091
296 Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial MTHFD2 0.009
1245 Vitamin K-dependent protein S PROS1 0.009
422 Vitamin K-dependent protein C PROC 0.009
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 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
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0085
13 Aminomethyltransferase, mitochondrial AMT 0.0084
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0084
5718 Cytochrome P450 2A6 CYP2A6 0.0083
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
3884 SHMT2 protein SHMT2 0.0081
3901 SHMT2 protein SHMT2 0.0081
3885 Hypothetical protein DKFZp686P09201 DKFZp686P09201 0.0081
3879 Serine hydroxymethyltransferase 2 Not Available 0.0081
321 Serine hydroxymethyltransferase, mitochondrial SHMT2 0.0081
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0081
448 Vitamin K-dependent gamma-carboxylase GGCX 0.008
6151 Monocarboxylate transporter 10 SLC16A10 0.008
4924 Cytochrome P450 2C8 CYP2C8 0.0079
914 Formimidoyltransferase-cyclodeaminase FTCD 0.0079
20 Prostaglandin G/H synthase 1 PTGS1 0.0078
4200 Cytochrome P450 1A2 CYP1A2 0.0076
4785 Ig gamma-1 chain C region IGHG1 0.0074
679 C-1-tetrahydrofolate synthase, cytoplasmic MTHFD1 0.0074
3639 Thymidine phosphorylase deoA 0.0073
3936 Thymidine phosphorylase TYMP 0.0073
798 Osteocalcin BGLAP 0.0071
5818 Folate receptor alpha FOLR1 0.0071
318 Alpha-2A adrenergic receptor ADRA2A 0.0071
367 Serine hydroxymethyltransferase, cytosolic SHMT1 0.0069
1302 Dihydropyrimidine dehydrogenase [NADP+] DPYD 0.0068
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
2795 Methionine aminopeptidase 2 METAP2 0.0066
787 Vitamin K epoxide reductase complex subunit 1 VKORC1 0.0066
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0065
369 Coagulation factor VII F7 0.0062
474 Acetylcholinesterase ACHE 0.006
6136 Multidrug resistance-associated protein 5 ABCC5 0.006
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0059
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0059
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0056
632 Alpha-1B adrenergic receptor ADRA1B 0.0056
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0053
5482 Sialidase-2 NEU2 0.0052
3947 Xanthine dehydrogenase/oxidase XDH 0.005
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.005
556 Alpha-1A adrenergic receptor ADRA1A 0.005
6024 Cytochrome P450 1A1 CYP1A1 0.0049
6106 Cytochrome P450 2C18 CYP2C18 0.0048
833 Organic cation/carnitine transporter 1 SLC22A4 0.0048
862 Multidrug resistance-associated protein 1 ABCC1 0.0047
2461 D-alanyl-D-alanine carboxypeptidase Not Available 0.0046
5756 D-alanyl-D-alanine carboxypeptidase dac 0.0046
239 Coagulation factor X F10 0.0046
3961 G protein-activated inward rectifier potassium channel 4 KCNJ5 0.0046
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0045
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.004
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0039
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0038
54 Prothrombin F2 0.0038
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0036
6148 Multidrug resistance-associated protein 7 ABCC10 0.0036
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
365 Dihydrofolate reductase DHFR 0.0032
2381 Dihydrofolate reductase DFR1 0.0032
2833 Dihydrofolate reductase Not Available 0.0032
2931 Dihydrofolate reductase folA 0.0032
3544 Dihydrofolate reductase folA 0.0032
3682 Dihydrofolate reductase folA 0.0032
6642 Dihydrofolate reductase folA 0.0032
6756 Dihydrofolate reductase dfrA 0.0032
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
432 D(4) dopamine receptor DRD4 0.0023
638 D(3) dopamine receptor DRD3 0.0022
776 Bile salt export pump ABCB11 0.0022
23 D(1A) dopamine receptor DRD1 0.002
831 D(2) dopamine receptor DRD2 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
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0014
6030 Cytochrome P450 2B6 CYP2B6 0.0011
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