Page last updated: 2024-12-06

perindoprilat

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Perindoprilat is a potent, competitive, and highly specific inhibitor of angiotensin-converting enzyme (ACE). It is a prodrug that is converted to its active form, perindopril, in the body. Perindoprilat has been studied extensively for its potential to treat hypertension, heart failure, and other cardiovascular diseases. Its effects are attributed to its ability to block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, decreased blood pressure, and reduced cardiac workload. Perindoprilat is also known to have anti-inflammatory and anti-proliferative effects, which may contribute to its cardiovascular benefits. Its importance lies in its efficacy in managing hypertension and other cardiovascular conditions. It has been shown to reduce the risk of cardiovascular events, including stroke, myocardial infarction, and death. The ongoing research on perindoprilat focuses on investigating its potential for treating other diseases, such as diabetic nephropathy and Alzheimer's disease.'

perindoprilat : A dipeptide obtained by formal condensation of one of the carboxy groups of N-[(1S)-1-carboxyethyl]-L-norvaline with the amino group of (2S,3aS,7aS)-octahydroindole-2-carboxylic acid. The major active metabolite of perindopril. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID72022
CHEMBL ID1201368
CHEBI ID132041
SCHEMBL ID564053
MeSH IDM0151553

Synonyms (58)

Synonym
(2s,3as,7as)-1-[(2s)-2-{[(1s)-1-carboxybutyl]amino}propanoyl]octahydro-1h-indole-2-carboxylic acid
CHEBI:132041 ,
perondropilat
perindoprilato
95153-31-4
perindoprilate
n-{(2s)-1-[(2s,3as,7as)-2-carboxyoctahydro-1h-indol-1-yl]-1-oxopropan-2-yl}-l-norvaline
perindoprilatum
perindopril diacid form
CHEMBL1201368
brn 4207072
s-9780
1h-indole-2-carboxylic acid, octahydro-1-(2-((1-carboxybutyl)amino)-1-oxopropyl)-, (2s-(1(r*(r*)),2-alpha,3a-beta,7a-beta))-
perindoprilat
perindoprilato [spanish]
(2s,3as,7as)-1-((s)-n-((s)-1-carboxybutyl)alanyl)hexahydro-2-indolinecarboxylic acid
s 9780
perindoprilatum [latin]
perindoprilate [french]
(2s,3as,7as)-1-[(2s)-2-[[(2s)-1-hydroxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid
(2s,3as,7as)-1-[(2s)-2-[[(1s)-1-carboxybutyl]amino]-1-oxopropyl]octahydro-1h-indole-2-carboxylic acid
perindoprilat [inn:ban]
unii-2uv6znq92k
2uv6znq92k ,
perindopril diacid form [mi]
perindopril tert-butylamine impurity b [ep impurity]
perindoprilat [inn]
gtpl6373
SCHEMBL564053
CCG-213925
(2s,3as,7as)-1-[(2s)-2-[[(1s)-1-carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid
(2s,3as,7as)-1-((s)-2-(((s)-1-carboxybutyl)amino)propanoyl)octahydro-1h-indole-2-carboxylic acid
AB01563365_01
AKOS026750118
C21517
(2s,3as,7as)-1-[(2s)-2-[[(2s)-1-hydroxy-1-oxopentan-2-yl]amino] propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid
ODAIHABQVKJNIY-PEDHHIEDSA-N
perondroprilat
NCGC00389603-01
x94 ,
A1-06488
(2s,3as,7as)-1-[(2s)-2-{[(1s)-1-carboxybutyl]amino}propanoyl]octahydro-1h-indole-2-carboxylic acid (non-preferred name)
DTXSID90869249 ,
(2s,3as,7as)-1-(((s)-1-carboxybutyl)-l-alanyl)octahydro-1h-indole-2-carboxylic acid
DB14213
Q27088302
[2s-[1[r*(r*)],2alpha,3abeta,7abeta]]-1-[2-[(1-carboxybutyl)amino]-1-oxopropyl]octahydro-1h-indole-2-carboxylic acid
(2s,3as,7as)-1-((s)-2-(((s)-1-carboxybutyl)amino)propanoyl)octahydro-1h-indole-2-carboxylicacid
discontinued. please see p287531 or p287535 or p287585.
HY-B1433
CS-0013140
perindoprilatum (latin)
n-((2s)-1-((2s,3as,7as)-2-carboxyoctahydro-1h-indol-1-yl)-1-oxopropan-2-yl)-l-norvaline
dtxcid10820872
(2s,3as,7as)-1-((2s)-2-(((1s)-1-carboxybutyl)amino)propanoyl)octahydro-1h-indole-2-carboxylic acid
perindopril tert-butylamine impurity b (ep impurity)
1h-indole-2-carboxylic acid, 1-[(2s)-2-[[(1s)-1-carboxybutyl]amino]-1-oxopropyl]octahydro-, (2s,3as,7as)-; 1h-indole-2-carboxylic acid, 1-[2-[(1-carboxybutyl)amino]-1-oxopropyl]octahydro-, [2s-[1[r*(r*)],2?,3a?,7a?]]-; perindoprilat; s 9780; perindopril r
(2s,3as,7as)-1-[(2s)-2-[[(1s)-1-carboxybutyl]amino]propanoyl]octahydro-1h-indole-2-carboxylic acid (perindoprilat)

Research Excerpts

Effects

ExcerptReferenceRelevance
"Perindoprilat has an additional inhibitory effect on the activity of acetylcholinesterase, whereas laser irradiation causes an increase in the activity of the enzyme."( Effect of combined treatment with perindoprilat and low-power red light laser irradiation on human erythrocyte membrane fluidity, membrane potential and acetylcholinesterase activity.
Bryszewska, M; Krajewska, E; Leyko, W; Piasecka, A, 2000
)
1.31
"Perindoprilat has an additional inhibitory effect on the activity of acetylcholinesterase, whereas laser irradiation causes an increase in the activity of the enzyme."( Effect of combined treatment with perindoprilat and low-power red light laser irradiation on human erythrocyte membrane fluidity, membrane potential and acetylcholinesterase activity.
Bryszewska, M; Krajewska, E; Leyko, W; Piasecka, A, 2000
)
1.31

Actions

ExcerptReferenceRelevance
"Perindoprilat induced an increase in cardiac index, stroke volume and heart rate."( [The effect of perindoprilat on the cardiovascular system of rats with heart failure].
Allabergenova, EA; Gorodetskaia, EA; Medvedev, OS; Moleva, EB,
)
1.21

Treatment

Perindoprilat treatment also significantly suppressed angiotensin II production in vitro.

ExcerptReferenceRelevance
"Perindoprilat pretreatment of renal arteries resulted, as expected, in decrease of ANG II production."( Perindoprilat changes ANG (1-9) production in renal arteries isolated from young spontaneously hypertensive rats after ANG I incubation.
Bujak-Giżycka, B; Jawień, J; Korbut, R; Madej, J; Olszanecki, R; Rutowski, J; Wołkow, PP, 2016
)
2.6
"Perindoprilat treatment also significantly suppressed angiotensin II production in vitro."( Effects of the angiotensin-I converting enzyme inhibitor perindopril on tumor growth and angiogenesis in head and neck squamous cell carcinoma cells.
Ito, A; Komune, S; Kuratomi, Y; Masuda, M; Nakagawa, T; Nakashima, T; Yasumatsu, R, 2004
)
1.04

Pharmacokinetics

The aim of the study was to develop a pharmacokinetic model for perindoprilat based on three phase I studies. 20 healthy Chinese subjects (16 males and 4 females) were enrolled and had their plasma concentrations of each drug quantified. Plasma concentrations of perindobrilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perIndopril.

ExcerptReferenceRelevance
" The pharmacokinetic parameters of perindopril, perindoprilat and perindoprilat glucuronide were evaluated after single administration to healthy volunteers (N = 12) of 8 mg of perindopril tert-butylamine salt by oral route (treatment A), by intravenous route (bolus in 5 min, treatment B) and of an equimolar dose of perindoprilat (6."( Pharmacokinetics of perindopril and its metabolites in healthy volunteers.
Ammoury, N; Devissaguet, JP; Devissaguet, M; Perret, L, 1990
)
0.53
" Plasma concentrations of perindoprilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perindopril."( Pharmacokinetics of perindopril: therapeutic consequences.
Hughes, DM; Lees, KR; McNeill, CA; Reid, JL, 1989
)
0.58
" The elimination half-life for free drug in plasma was only 30 min."( Pharmacokinetics of an ACE inhibitor, S-9780, in man: evidence of tissue binding.
Kelman, AW; Lees, KR; Reid, JL; Whiting, B, 1989
)
0.28
" Cmax and AUC tended to be higher after the 4 mg dose in the Chinese group who had a lower body weight than the Caucasians."( Comparison of the pharmacokinetics and pharmacodynamics of oral doses of perindopril in normotensive Chinese and Caucasian volunteers.
Anderson, PJ; Critchley, JA; Resplandy, G; Tomlinson, B, 1995
)
0.29
"The purpose of the present report was to develop a pharmacokinetic model for perindoprilat based on three phase I studies including administration of oral and intravenous perindopril and administration of intravenous perindoprilat."( The pharmacokinetics of perindoprilat in normal volunteers and patients: influence of age and disease state.
Aarons, L; Parker, E; Resplandy, G; Rowland, M, 2005
)
0.86
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35
"To investigate the pharmacokinetic parameters of perindopril and perindoprilat in healthy volunteers, a simple and sensitive UPLC-MS/MS method with isotope-labeled internal standards of perindopril-d4 and perindoprilat-d4 was established and further applied in a bioequivalence study."( A UPLC-MS/MS method for quantification of perindopril and perindoprilat and applied in a bioequivalence study for their pharmacokinetic parameter measurement
.
Cai, H; Gu, Y; Guo, J; He, B; Huang, X; Liu, X; Tan, X; Wei, W; Yang, H; Yin, Y; Zhang, B; Zhou, X, 2020
)
1.04
" 20 healthy Chinese subjects (16 males and 4 females) were enrolled and had their plasma concentrations of perindopril and perindoprilat quantified and calculated for the pharmacokinetic parameters."( A UPLC-MS/MS method for quantification of perindopril and perindoprilat and applied in a bioequivalence study for their pharmacokinetic parameter measurement
.
Cai, H; Gu, Y; Guo, J; He, B; Huang, X; Liu, X; Tan, X; Wei, W; Yang, H; Yin, Y; Zhang, B; Zhou, X, 2020
)
1.01

Bioavailability

ExcerptReferenceRelevance
" Perindopril is rapidly absorbed with an oral bioavailability of 95% and is mainly eliminated by metabolic processes."( Pharmacokinetics of perindopril and its metabolites in healthy volunteers.
Ammoury, N; Devissaguet, JP; Devissaguet, M; Perret, L, 1990
)
0.28
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindobrilat. No dosage adjustment is required in cirrhotic patients, we say.

ExcerptRelevanceReference
" We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients."( The pharmacokinetics of perindopril in patients with liver cirrhosis.
Funck-Brentano, C; Grangé, JD; Jaillon, P; Midavaine, M; Resplandy, G; Thiollet, M, 1992
)
0.49
" 8 In view of the important influence of renal impairment on the elimination and action of the active substance perindoprilat, a dosage reduction of perindopril is proposed in in patients with renal failure."( Single dose pharmacokinetics of perindopril and its metabolites in hypertensive patients with various degrees of renal insufficiency.
De Broe, ME; Genissel, PM; Thomas, JR; Verpooten, GA, 1991
)
0.49
" As it has been shown that the kinetics of perindoprilat are mainly affected by renal insufficiency, a dosage reduction is therefore recommended on initiation of treatment in elderly patients and in those with renal failure according to the degree of renal failure."( Pharmacokinetics of perindopril in high-risk populations.
Genissel, P; Resplandy, G, 1991
)
0.54
" During repeated dosing there is little accumulation of drug, and no evidence of increased haemodynamic effect after chronic treatment in hypertensives."( Pharmacokinetics of perindopril: therapeutic consequences.
Hughes, DM; Lees, KR; McNeill, CA; Reid, JL, 1989
)
0.28
" Oral dosing with active drugs led to different temporal responses."( Blood pressure response to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure.
Lees, KR; MacFadyen, RJ; Reid, JL; Squire, IB, 1993
)
0.29
" The mean slope of the FABF (log transformed) versus norepinephrine dose-response curve was significantly attenuated by perindoprilat compared with placebo (-0."( ACE inhibition: postsynaptic adrenergic sympatholytic action in men.
Lyons, D; O'Byrne, S; Roy, S; Swift, CG, 1997
)
0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
antihypertensive agentAny drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism.
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitorAn EC 3.4.15.* (peptidyl-dipeptidase) inhibitor that interferes with the action of peptidyl-dipeptidase A (EC 3.4.15.1).
drug metabolitenull
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (4)

ClassDescription
organic heterobicyclic compound
dipeptideAny molecule that contains two amino-acid residues connected by peptide linkages.
dicarboxylic acidAny carboxylic acid containing two carboxy groups.
L-alanine derivativeA proteinogenic amino acid derivative resulting from reaction of L-alanine at the amino group or the carboxy group, or from the replacement of any hydrogen of L-alanine by a heteroatom.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (1)

PathwayProteinsCompounds
Perindopril Action Pathway35

Bioassays (12)

Assay IDTitleYearJournalArticle
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID679608TP_TRANSPORTER: inhibition of Digoxin transepithelial transport (basal to apical) (Digoxin: 0.1 uM, Perindoprilat: 50 uM) in MDR1-expressing LLC-PK1 cells2002Life sciences, Feb-15, Volume: 70, Issue:13
Interaction of digoxin with antihypertensive drugs via MDR1.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1345457Human Angiotensin-converting enzyme (M2: Angiotensin-converting (ACE and ACE2))2007European journal of pharmacology, Dec-22, Volume: 577, Issue:1-3
Angiotensin-converting enzyme (ACE) inhibitors have different selectivity for bradykinin binding sites of human somatic ACE.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (111)

TimeframeStudies, This Drug (%)All Drugs %
pre-19908 (7.21)18.7374
1990's60 (54.05)18.2507
2000's27 (24.32)29.6817
2010's10 (9.01)24.3611
2020's6 (5.41)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 27.43

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index27.43 (24.57)
Research Supply Index4.96 (2.92)
Research Growth Index5.20 (4.65)
Search Engine Demand Index34.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (27.43)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials25 (21.55%)5.53%
Reviews4 (3.45%)6.00%
Case Studies1 (0.86%)4.05%
Observational1 (0.86%)0.25%
Other85 (73.28%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]