General
Preferred name
EFONIDIPINE
Synonyms
Efonidipine hydrochloride monoethanolate ()
Efonidipine (hydrochloride) ()
NZ-105 hydrochloride ()
(¡À)-Efonidipine ()
NZ-105 hydrochloride monoethanolate ()
(??)-Efonidipine ()
NZ-105 ()
Efonidipine (hydrochloride monoethanolate) ()
EFONIDIPINE HCL ()
Efonidipine hydrochloride ()
P&D ID
PD008991
CAS
111011-76-8
111011-63-3
111011-53-1
Tags
available
drug
Drug Status
experimental
approved
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA
This drug inhibits the L-type and T-type calcium channels, thereby leading to vasodilation and decreased automaticity of the heart. Efonidipine exerts negative chronotropic effects, decreasing heart rate. Acting on SA node cells by inhibiting T-type calcium channel activity, Efonidipine prolongs the late phase-4 depolarization of the sinoatrial node action potential, decreasing heart rate. This is associated with decreased myocardial oxygen demand and increases of blood flow to the coronary arteries and thereby attenuates myocardial ischemia. Efonidipine increases glomerular filtration rate (GFR) without increasing intra-glomerular pressure and filtration fraction [A7844, A32003, A32010] . This increase leads to the prevention of renal damage that is normally associated with hypertension.; ; Efonidipine increases the rate of renal sodium excretion via the suppression of aldosterone synthesis and aldosterone secretion from the adrenal glands. Aldosterone-induced renal parenchymal fibrosis is said to be suppressed by efonidipine [A32010].; ; L-type calcium channel blockers, such as efonidipine, preferentially dilate afferent arterioles in the kidney, whereas both L-/T-type and L-/N-type calcium channel blockers potently dilate both afferent and efferent arterioles. The distinct actions of calcium channel blockers on the renal microcirculation are demonstrated by changes in glomerular capillary pressure and subsequent renal injury: L-type calcium channel blockers favor an increase in glomerular capillary pressure, whereas L-/T-type and L-/N-type CCBs alleviate glomerular hypertension. This supports the theory that L-Type/T-type calcium channel blockers may be of benefit in renal hypertension [A32010]. Efonidipine is a long-acting medication due to a low dissociation constant [L1449]. ; ; Recent studies suggest that efonidipine reduces plasma aldosterone levels in patients on regular hemodialysis, which is of additional benefit to the cardiovascular protection by antihypertensive therapy with efonidipine in patients with end-stage renal disease [L1437].
TOXICITY
Ld50: >5 g/kg in rats, orally [L1441, L1459].; Some common adverse effects include hot flashes, flushing of the face, and headache. Elevation in serum total cholesterol, ALT (SGPT), AST (SGOT) and BUN may also occur. Frequent urination, pedal edema, increased triglycerides have been found to occur in less than 0.1% of patients [L1460, L1459].
HALF-LIFE
The peak plasma concentration is attained at approximately 1.5 to 3.67 hours after ingestion. The half-life is measured to be about 4 hours [L1450].
METABOLISM
It has been suggested that efonidipine is less likely to be subject to the first-pass than other members of its drug class, and and that its dihydropyridine ring is oxidized primarily after metabolism of the side chain [L1443]. Efonidipine is highly lipophilic and this allows for its entry into the phospholipid-rich cell membrane and reach the dihydropyridine binding site of the calcium channel targets [L1446].; ; Efonidipine is mainly metabolized in the liver. Its metabolites are N-dephenylated Efonidipine (DPH), deaminated efonidipine (AL) and N-debenzylated Efonidipine (DBZ). Both metabolites behave as calcium antagonists. In one study, the vasodilating capabilities of DBZ and DPH were about two-thirds and one-third respectively than that of the unmetabolized drug. Research suggests that the majority of the pharmacological effect after oral dosing of efonidipine hydrochloride is due to unchanged drug and its metabolites play little role in its therapeutic effect.; ; In a study of six healthy volunteers, no significant amount of unchanged drug was excreted in urine. The urine samples collected for 24âh after oral efonidipine administration, 1.1% of the dose was excreted as deaminated-efonidipine, and 0.5% as a pyridine analogue of deaminated-efonidipine [L1457].
ABSORPTION
The metabolism of efonidipine was studied in rats. The absorption ratio of radioactivity estimated from the sum of biliary and urinary excretions was found to be approximately 62% [L1457]. The radioactivity was high in the gastrointestinal tract and liver, followed by the adrenal glands [L1457], suggesting high rates of metabolism in these regions. ; ; The unchanged drug in the plasma accounted for 47.7% of radioactivity at 2hr after ingestion, demonstrating a lower first-pass effect in comparison with other drugs in the same class. In plasma, major metabolites of NZ-105 were: N-debenzylated compound (DBZ), N-dephenylated compound (DPH), oxidative deaminated compound (AL), AL-corresponding pyridine compound (ALP), unknown metabolite M-1 and M-25. NZ-105 was metabolized by N-debenzylation, N-dephenylation, oxidative deamination, ester hydrolysis and oxidation of 1, 4-dihydropyridine ring to its corresponding pyridine [L1457].; ;
DESCRIPTION
This version of efonidipine's chemical structure without stereo bond details is used to represent the racemic mixture that is defined by the INN. Efonidipine is a dihydropyridine class calcium channel blocker that inhibits L-type and T-type calcium channels .
(GtoPdb)
DESCRIPTION
Ca2+ channel blocker (L- and T-type)
(Tocriscreen Total)
DESCRIPTION
The hydrochloride monoethanolate salt form of Efonidipine which has been launched for hypertension and discontinued for cerebrovascular disorders.
(BOC Sciences Bioactive Compounds)
DESCRIPTION
Ca2+ channel blocker (L- and T-type)
(Tocriscreen Plus)
DESCRIPTION
Efonidipine could be effective in the treatment of cardiovascular disease as a blocker of T-type and L-type calcium channels. It could also present as the hydrochloride salt form.
(BOC Sciences Bioactive Compounds)
DESCRIPTION
The hydrochloride salt form of Efonidipine which could be effective in the treatment of cardiovascular disease as a blocker of T-type and L-type calcium channels.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
16
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Drugs
Concise Guide to Pharmacology 2023/24
DrugBank
DrugCentral
DrugCentral Approved Drugs
DrugMatrix
Guide to Pharmacology
MedChem Express Bioactive Compound Library
NPC Screening Collection
ReFrame library
Selleckchem Bioactive Compound Library
Tocriscreen Plus
Tocriscreen Total
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
43
Molecular Weight
631.24
Hydrogen Bond Acceptors
9
Hydrogen Bond Donors
1
Rotatable Bonds
10
Ring Count
5
Aromatic Ring Count
3
cLogP
7.3
TPSA
120.24
Fraction CSP3
0.32
Chiral centers
1.0
Largest ring
6.0
QED
0.11
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Ion Channels
Target
Calcium Channel
Pathway
Membrane Transporter/Ion Channel
Neuronal Signaling
Solubility
10 mM in DMSO
in DMSO > 10 Mm
DMSO: ≥ 8.5 mg/mL
Source data
