General
Preferred name
OLMESARTAN
Synonyms
Olmesartan D4 ()
RNH-6270 D4 ()
CS-088 D4 ()
RNH 6270 ()
CS 088 ()
RNH-6270 ()
Olmesartan medoxomil impurity, olmesartan- ()
NSC-759810 ()
Olmesartan-d6 ()
P&D ID
PD000566
CAS
144689-24-7
1185144-74-4
Tags
natural product
drug
available
Drug Status
investigational
approved
Max Phase
Phase 3
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE The mean plasma olmesartan half-life is reported to be from 10-15 hours after multiple oral administration.[A175330]
ROE The main elimination route of olmesartan is in the unchanged form through the feces. From the systemically bioavailable dose, about 10-16% is eliminated in the urine.[A175330]
MOA Olmesartan is a selective angiotensin II-type I receptor blocker with a large affinity. It has been shown to present an IC50 of 8 nmol/L while showing a very minimal affinity towards angiotensin-II type II receptor. The blockage of olmesartan is done by the displacement of angiotensin II converting it hence, in a competitive antagonist.[A175330] The activity of olmesartan is mainly performed in vascular smooth muscle cells and hence its activity prevents the vasoconstrictor effects of angiotensin II.[A175342]
INDICATION Olmesartan is indicated for the treatment of hypertension either alone or associated with other antihypertensive agents.[FDA label] Hypertension is a sustained elevation of resting blood pressure. The hypertensive effect can affect the systolic blood pressure, diastolic blood pressure or both. This condition tends to be asymptomatic until it reaches a severe or long-standing state.[L5569]
TOXICITY The reported LD50 of olmesartan in dogs was reported to be greater of 1500 mg/kg. Overdose is expressed as hypotension, tachycardia, and bradycardia when there is parasympathetic stimulation. In case of overdose, supportive treatment is recommended.[FDA label] Olmesartan was shown to be safe on carcinogenic and fertility studies. However, in _in vitro_ mutagenic studies showed a potential to induce chromosomal aberrations in cells and it tested positive for thymidine kinase mutations in the mouse lymphoma assay.[FDA label]
TOXICITY The reported LD50 of olmesartan in dogs was reported to be greater of 1500 mg/kg. Overdose is expressed as hypotension, tachycardia, and bradycardia when there is parasympathetic stimulation. In case of overdose, supportive treatment is recommended.[FDA label]; ; Olmesartan was shown to be safe on carcinogenic and fertility studies. However, in _in vitro_ mutagenic studies showed a potential to induce chromosomal aberrations in cells and it tested positive for thymidine kinase mutations in the mouse lymphoma assay.[FDA label]
MOA Olmesartan is a selective angiotensin II-type I receptor blocker with a large affinity. It has been shown to present an IC50 of 8 nmol/L while showing a very minimal affinity towards angiotensin-II type II receptor. The blockage of olmesartan is done by the displacement of angiotensin II converting it hence, in a competitive antagonist.[A175330] ; ; The activity of olmesartan is mainly performed in vascular smooth muscle cells and hence its activity prevents the vasoconstrictor effects of angiotensin II.[A175342]
INDICATION Olmesartan is indicated for the treatment of hypertension either alone or associated with other antihypertensive agents.[FDA label]; ; Hypertension is a sustained elevation of resting blood pressure. The hypertensive effect can affect the systolic blood pressure, diastolic blood pressure or both. This condition tends to be asymptomatic until it reaches a severe or long-standing state.[L5569]
METABOLISM Olmesartan is rapidly and completely bioactivated by ester hydrolysis to olmesartan during absorption from the gastrointestinal tract. This rapid first-pass metabolism was confirmed by the lack of measurable amounts of olmesartan medoxomil in plasma or excreta.[A175330] This first-pass metabolism is not driven by cytochrome enzymes and hence it is not expected to interact with other drugs via this mechanism.[A175342]; ; The pharmacologically active moiety has shown to not present further metabolism.[A175330]
ABSORPTION Olmesartan, in the form of olmesartan medoxomil is rapidly absorbed in the gastrointestinal tract and metabolized to olmesartan. The esterification with medoxomil was created with the intention of increasing olmesartan bioavailability from 4.5% to 28.6%.[A175330]; ; Oral administration of 10-160 mg of olmesartan has been shown to reach peak plasma concentration of 0.22-2.1 mg/L after 1-3 hours with an AUC of 1.6-19.9mgh/L.[A175342] The pharmacokinetic profile of olmesartan has been observed to be nearly linear and dose-dependent under the therapeutic range.[A175330] The steady-state level of olmesartan is achieved after once a day dosing during 3 to 5 days.[L5566]
METABOLISM Olmesartan is rapidly and completely bioactivated by ester hydrolysis to olmesartan during absorption from the gastrointestinal tract. This rapid first-pass metabolism was confirmed by the lack of measurable amounts of olmesartan medoxomil in plasma or excreta.[A175330] This first-pass metabolism is not driven by cytochrome enzymes and hence it is not expected to interact with other drugs via this mechanism.[A175342] The pharmacologically active moiety has shown to not present further metabolism.[A175330]
PHARMACODYNAMICS The activities of olmesartan directly antagonize the angiotensin-mediated contraction in a dose-dependent manner. The activity of olmesartan can produce inhibition of 90% of the muscle contractility for at least 90 minutes.[A175342] Preclinical studies driven by inhibition of nitric oxide synthesis showed that olmesartan inhibits the angiotensin II-induced pressor response which in order prevents the production of markers of early cardiovascular inflammation, myocardial remodeling, and cardiac fibrosis. It also reduced the protein urinary secretion, the area of aortic plaque lesions and the intimal thickening in cross-sections of the aorta.[A175342] In clinical trials made on hypertensive patients following a low-sodium diet, olmesartan was observed to significantly decrease diastolic blood pressure when compared with placebo-treated patients.[A175330] As well, the administration of olmesartan was shown to lower the mean 24 hours ambulatory blood pressure and to increase renin and angiotensin II concentrations in plasma.[A175342]
ABSORPTION Olmesartan, in the form of olmesartan medoxomil is rapidly absorbed in the gastrointestinal tract and metabolized to olmesartan. The esterification with medoxomil was created with the intention of increasing olmesartan bioavailability from 4.5% to 28.6%.[A175330] Oral administration of 10-160 mg of olmesartan has been shown to reach peak plasma concentration of 0.22-2.1 mg/L after 1-3 hours with an AUC of 1.6-19.9mgh/L.[A175342] The pharmacokinetic profile of olmesartan has been observed to be nearly linear and dose-dependent under the therapeutic range.[A175330] The steady-state level of olmesartan is achieved after once a day dosing during 3 to 5 days.[L5566]
PHARMACODYNAMICS The activities of olmesartan directly antagonize the angiotensin-mediated contraction in a dose-dependent manner. The activity of olmesartan can produce inhibition of 90% of the muscle contractility for at least 90 minutes.[A175342]; ; Preclinical studies driven by inhibition of nitric oxide synthesis showed that olmesartan inhibits the angiotensin II-induced pressor response which in order prevents the production of markers of early cardiovascular inflammation, myocardial remodeling, and cardiac fibrosis. It also reduced the protein urinary secretion, the area of aortic plaque lesions and the intimal thickening in cross-sections of the aorta.[A175342]; ; In clinical trials made on hypertensive patients following a low-sodium diet, olmesartan was observed to significantly decrease diastolic blood pressure when compared with placebo-treated patients.[A175330] As well, the administration of olmesartan was shown to lower the mean 24 hours ambulatory blood pressure and to increase renin and angiotensin II concentrations in plasma.[A175342]
DESCRIPTION Potent and selective GPR109A (HCA2) agonist (Tocris Bioactive Compound Library)
DESCRIPTION Potent AT1 antagonist; metabolite of Olmesartan medoxomil (Cat. No. 4620) (Tocriscreen Plus)
Compound Sets
17
Axon Medchem Screening Library
3105
Cayman Chemical Bioactives
23412
36324
ChEMBL Drugs
CHEMBL1516
Drug Repurposing Hub
DrugBank
DB00275
DrugBank Approved Drugs
DB00275
Enamine BioReference Compounds
MedChem Express Bioactive Compound Library
HY-17004
NCATS Inxight Approved Drugs
8W1IQP3U10
NIH Clinical Collections (NCC)
Other bioactive compounds
ReFrame library
Selleckchem Bioactive Compound Library
olmesartan
TargetMol Bioactive Compound Library
T5964
The Spectrum Collection
Tocris Bioactive Compound Library
4616
Tocriscreen Plus
4616
External IDs
48
Properties
(calculated by RDKit )
Molecular Weight
446.21
Hydrogen Bond Acceptors
7
Hydrogen Bond Donors
3
Rotatable Bonds
8
Ring Count
4
Aromatic Ring Count
4
cLogP
3.66
TPSA
129.81
Fraction CSP3
0.29
Chiral centers
0.0
Largest ring
6.0
QED
0.38
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Target
Angiotensin Receptor
angiotensin II receptor
AGTR1
AT1 antagonist
Pathway
GPCR/G protein
Endocrinology/Hormones
Primary Target
Angiotensin AT1 Receptors
MOA
Antagonist
angiotensin receptor antagonist
Indication
hypertension
Source data