Identification

Name
Benidipine
Accession Number
DB09231
Type
Small Molecule
Groups
Approved, Investigational
Description

Benidipine has the formula 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid methyl 1-(phenylmethyl)-3-piperidinyl ester hydrochloride. It is a synthetic dihydropyridine derivative that has anti-hypertensive and anti-anginal actions.[1] It was originated in Japan by Kyowa Hakko, it is submitted for FDA approval and it is currently available in some Asian countries like India and Japan.[4, 5]

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Benidipine hydrochloride0A6746FWDL91599-74-5KILKDKRQBYMKQX-MIPPOABVSA-N
International/Other Brands
Coniel (Kyowa Hakko Kogyo)
Categories
UNII
4G9T91JS7E
CAS number
105979-17-7
Weight
Average: 505.571
Monoisotopic: 505.22128573
Chemical Formula
C28H31N3O6
InChI Key
QZVNQOLPLYWLHQ-ZEQKJWHPSA-N
InChI
InChI=1S/C28H31N3O6/c1-18-24(27(32)36-3)26(21-11-7-12-22(15-21)31(34)35)25(19(2)29-18)28(33)37-23-13-8-14-30(17-23)16-20-9-5-4-6-10-20/h4-7,9-12,15,23,26,29H,8,13-14,16-17H2,1-3H3/t23-,26-/m1/s1
IUPAC Name
3-(3R)-1-benzylpiperidin-3-yl 5-methyl (4R)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
COC(=O)C1=C(C)NC(C)=C([[email protected]@H]1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)O[[email protected]@H]1CCCN(CC2=CC=CC=C2)C1

Pharmacology

Indication

Benidipine is a potent and long-lasting drug indicated for the treatment of cardiovascular diseases such as hypertension, renoparenchymal hypertension and angina pectoris.[2]

Structured Indications
Not Available
Pharmacodynamics

Benidipine reduces systolic and diastolic blood pressure as well as to present decreases in heart rate pulse after treatment. It is reported also a decrease urinary protein excretion and serum triglycerides.[4] Different studies have shown benidipine anti-oxidative activity, stimulation of NO production, suppression of adhesion molecules expression, stimulation of osteoblast differentiation, suppression of the proliferation of vascular smooth muscle cells and mesangial cells, as well as myocardial protection. The enhancement of NO production is associated with the cardioprotective and antiartheriosclerotic effects of benidipine.[2]

Mechanism of action

Benidipine is a tripe calcium channel inhibitor by inhibiting L, N and T type calcium channel.[4] It presents a very long-lasting activity that can be explained by its high affinity for cell membranes from the DHP binding site; this characteristic indicated a long-lasting pharmacological activity of benidipine. The additional property of benidipine is the vascular selectivity towards peripheral blood vessels.[2]

TargetActionsOrganism
AVoltage dependent L type calcium channel
antagonist
Human
AVoltage-dependent N-type calcium channel subunit alpha-1B
antagonist
Human
AVoltage-dependent T-type calcium channel
antagonist
Homo sapiens
Absorption

Benidipine is rapidly absorbed after oral administration reaching a maximum concentration within 2 hours. The short period of time needed for maximum concentration to get reached is a particular characteristic of benidipine when compared with other calcium channel blockers. The registered maximum concentration and AUC are dose-dependent and it can go from 0.55-3.89 ng/ml and 1.04-6.7 ng.h/ml respectively when administered in a dose of 2-8 mg.[2]

Volume of distribution

Benidipine is highly distributed to the tissues mainly in the liver and kidneys and plasma. It does not present a high accumulation following repeated oral administrations.[2]

Protein binding

Benidipine is highly bound to plasma proteins and the bound form can account for even 98% of the administered dose.[2]

Metabolism

Benidipine is almost completely metabolized in the liver. From different reports, it is thought that benidipine is mainly metabolized by CYP3A.[2] Some of the formed metabolites are N-desbenzylbenidipine and dehydrobenidipine. Analysis on the formation of metabolites has indicated that the metabolism is mainly performed by CYP3A4 and CYP3A5.[3]

Route of elimination

The percentage of urinary excretion after oral administration is of approximate 36% of the administered dose. Most of the remaining dose is excreted in feces, making bile excretion the major elimination pathway of benidipine. From the eliminated drug, none of it is expressed in the form of the unchanged drug.[2]

Half life

The elimination half-life of benidipine is registered to be of approximate 1 hour.[2]

Clearance
Not Available
Toxicity

In preclinical studies, the LD50 of benidipine ranged from 87-384 mg/kg which is more than 100 times the needed dose to achieve anti-hypertensive action. There were no significant changes in histopathological heart examination. Benidipine showed no carcinogenic, antigenicity, teratogenic or mutagenic properties.[2]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2-HYDROXY-1,4-NAPHTHOQUINONEThe therapeutic efficacy of 2-HYDROXY-1,4-NAPHTHOQUINONE can be increased when used in combination with Benidipine.Experimental
2-mercaptobenzothiazoleThe therapeutic efficacy of 2-mercaptobenzothiazole can be increased when used in combination with Benidipine.Vet Approved
AlfuzosinThe risk or severity of hypotension can be increased when Alfuzosin is combined with Benidipine.Approved, Investigational
AmiodaroneThe metabolism of Benidipine can be decreased when combined with Amiodarone.Approved, Investigational
AmobarbitalThe metabolism of Benidipine can be increased when combined with Amobarbital.Approved, Illicit
AmorolfineThe therapeutic efficacy of Amorolfine can be increased when used in combination with Benidipine.Approved, Investigational
Amphotericin BThe therapeutic efficacy of Amphotericin B can be increased when used in combination with Benidipine.Approved, Investigational
AnidulafunginThe therapeutic efficacy of Anidulafungin can be increased when used in combination with Benidipine.Approved, Investigational
ApalutamideThe serum concentration of Benidipine can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of Benidipine can be increased when it is combined with Aprepitant.Approved, Investigational
ArotinololThe risk or severity of hypotension, conduction block, and bradycardia can be increased when Arotinolol is combined with Benidipine.Investigational
ArtemetherThe therapeutic efficacy of Artemether can be increased when used in combination with Benidipine.Approved
AtazanavirThe metabolism of Benidipine can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Benidipine can be decreased when combined with Atomoxetine.Approved
Bafilomycin A1The therapeutic efficacy of Bafilomycin A1 can be increased when used in combination with Benidipine.Experimental
BarbexacloneThe metabolism of Benidipine can be increased when combined with Barbexaclone.Experimental
BarbitalThe metabolism of Benidipine can be increased when combined with Barbital.Illicit
Benzoic AcidThe therapeutic efficacy of Benzoic Acid can be increased when used in combination with Benidipine.Approved, Investigational
BifonazoleThe therapeutic efficacy of Bifonazole can be increased when used in combination with Benidipine.Approved, Investigational
BoceprevirThe metabolism of Benidipine can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Benidipine can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Benidipine can be decreased when it is combined with Bosentan.Approved, Investigational
Brefeldin AThe therapeutic efficacy of Brefeldin A can be increased when used in combination with Benidipine.Experimental
BucindololThe risk or severity of hypotension can be increased when Bucindolol is combined with Benidipine.Investigational
BunazosinThe risk or severity of hypotension can be increased when Bunazosin is combined with Benidipine.Investigational
ButenafineThe therapeutic efficacy of Butenafine can be increased when used in combination with Benidipine.Approved
ButoconazoleThe therapeutic efficacy of Butoconazole can be increased when used in combination with Benidipine.Approved
Calcium AcetateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium Acetate.Approved, Investigational
Calcium ChlorideThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium Chloride.Approved
Calcium CitrateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium Citrate.Approved
Calcium glubionateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium glubionate.Approved
Calcium GluceptateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium Gluceptate.Approved
Calcium gluconateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium gluconate.Approved, Vet Approved
Calcium lactateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium lactate.Approved, Experimental, Investigational, Vet Approved
Calcium lactate gluconateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium lactate gluconate.Experimental
Calcium levulinateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium levulinate.Approved, Experimental
Calcium pangamateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium pangamate.Experimental
Calcium PhosphateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium Phosphate.Approved
CandicidinThe therapeutic efficacy of Candicidin can be increased when used in combination with Benidipine.Withdrawn
Capric acidThe therapeutic efficacy of Capric acid can be increased when used in combination with Benidipine.Experimental
CarbamazepineThe metabolism of Benidipine can be increased when combined with Carbamazepine.Approved, Investigational
CarvedilolThe risk or severity of hypotension can be increased when Carvedilol is combined with Benidipine.Approved, Investigational
CaseinThe therapeutic efficacy of Benidipine can be decreased when used in combination with Casein.Approved
CaspofunginThe therapeutic efficacy of Caspofungin can be increased when used in combination with Benidipine.Approved
CeritinibThe serum concentration of Benidipine can be increased when it is combined with Ceritinib.Approved
CeruleninThe therapeutic efficacy of Cerulenin can be increased when used in combination with Benidipine.Approved
ChloroxineThe therapeutic efficacy of Chloroxine can be increased when used in combination with Benidipine.Approved
CiclopiroxThe therapeutic efficacy of Ciclopirox can be increased when used in combination with Benidipine.Approved, Investigational
CimetidineThe serum concentration of Benidipine can be increased when it is combined with Cimetidine.Approved, Investigational
ClarithromycinThe metabolism of Benidipine can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Benidipine can be decreased when combined with Clemastine.Approved, Investigational
ClopidogrelThe therapeutic efficacy of Clopidogrel can be decreased when used in combination with Benidipine.Approved
ClotrimazoleThe therapeutic efficacy of Clotrimazole can be increased when used in combination with Benidipine.Approved, Vet Approved
CobicistatThe metabolism of Benidipine can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Benidipine.Approved, Investigational
CordycepinThe therapeutic efficacy of Cordycepin can be increased when used in combination with Benidipine.Investigational
CrizotinibThe metabolism of Benidipine can be decreased when combined with Crizotinib.Approved
CyclosporineThe therapeutic efficacy of Cyclosporine can be increased when used in combination with Benidipine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Benidipine can be decreased when it is combined with Dabrafenib.Approved, Investigational
DarunavirThe metabolism of Benidipine can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Benidipine can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Benidipine can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Benidipine can be decreased when combined with Delavirdine.Approved
DichloropheneThe therapeutic efficacy of Dichlorophene can be increased when used in combination with Benidipine.Vet Approved
DihydroergotamineThe metabolism of Benidipine can be decreased when combined with Dihydroergotamine.Approved, Investigational
DiltiazemThe metabolism of Benidipine can be decreased when combined with Diltiazem.Approved, Investigational
DoxazosinThe risk or severity of hypotension can be increased when Doxazosin is combined with Benidipine.Approved
DoxycyclineThe metabolism of Benidipine can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Benidipine can be decreased when combined with Dronedarone.Approved
EconazoleThe therapeutic efficacy of Econazole can be increased when used in combination with Benidipine.Approved
EfavirenzThe serum concentration of Benidipine can be decreased when it is combined with Efavirenz.Approved, Investigational
EfinaconazoleThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Benidipine.Approved
EnzalutamideThe serum concentration of Benidipine can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Benidipine can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
FenticonazoleThe therapeutic efficacy of Fenticonazole can be increased when used in combination with Benidipine.Experimental
FluconazoleThe therapeutic efficacy of Fluconazole can be increased when used in combination with Benidipine.Approved, Investigational
FlucytosineThe therapeutic efficacy of Flucytosine can be increased when used in combination with Benidipine.Approved, Investigational
FlutrimazoleThe therapeutic efficacy of Flutrimazole can be increased when used in combination with Benidipine.Experimental
FluvoxamineThe metabolism of Benidipine can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Benidipine can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Benidipine can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Benidipine can be increased when combined with Fosphenytoin.Approved, Investigational
Fusidic AcidThe serum concentration of Benidipine can be increased when it is combined with Fusidic Acid.Approved, Investigational
GlyphosateThe therapeutic efficacy of Glyphosate can be increased when used in combination with Benidipine.Experimental
GriseofulvinThe therapeutic efficacy of Griseofulvin can be increased when used in combination with Benidipine.Approved, Investigational, Vet Approved
HachimycinThe therapeutic efficacy of Hachimycin can be increased when used in combination with Benidipine.Experimental
HaloproginThe therapeutic efficacy of Haloprogin can be increased when used in combination with Benidipine.Approved, Withdrawn
HexetidineThe therapeutic efficacy of Hexetidine can be increased when used in combination with Benidipine.Approved, Investigational
HexobarbitalThe metabolism of Benidipine can be increased when combined with Hexobarbital.Approved
IdelalisibThe metabolism of Benidipine can be decreased when combined with Idelalisib.Approved
ImatinibThe metabolism of Benidipine can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Benidipine can be decreased when combined with Indinavir.Approved
IndoraminThe risk or severity of hypotension can be increased when Indoramin is combined with Benidipine.Withdrawn
IsavuconazoleThe serum concentration of Benidipine can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Benidipine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoconazoleThe therapeutic efficacy of Isoconazole can be increased when used in combination with Benidipine.Approved
IsradipineThe metabolism of Benidipine can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe metabolism of Benidipine can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Benidipine can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Benidipine can be decreased when combined with Ketoconazole.Approved, Investigational
LabetalolThe risk or severity of hypotension can be increased when Labetalol is combined with Benidipine.Approved
LopinavirThe metabolism of Benidipine can be decreased when combined with Lopinavir.Approved
LorpiprazoleThe serum concentration of Benidipine can be increased when it is combined with Lorpiprazole.Approved
LovastatinThe metabolism of Benidipine can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Benidipine can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Benidipine can be decreased when it is combined with Lumacaftor.Approved
Magnesium hydroxideThe risk or severity of hypotension and neuromuscular blockade can be increased when Benidipine is combined with Magnesium hydroxide.Approved, Investigational
Magnesium oxideThe risk or severity of hypotension and neuromuscular blockade can be increased when Benidipine is combined with Magnesium oxide.Approved
Magnesium salicylateThe risk or severity of hypotension and neuromuscular blockade can be increased when Benidipine is combined with Magnesium salicylate.Approved
Magnesium sulfateThe risk or severity of hypotension and neuromuscular blockade can be increased when Benidipine is combined with Magnesium sulfate.Approved, Investigational, Vet Approved
MepartricinThe therapeutic efficacy of Mepartricin can be increased when used in combination with Benidipine.Experimental
MethohexitalThe metabolism of Benidipine can be increased when combined with Methohexital.Approved
MethylphenobarbitalThe metabolism of Benidipine can be increased when combined with Methylphenobarbital.Approved
MevastatinThe therapeutic efficacy of Mevastatin can be increased when used in combination with Benidipine.Experimental
MicafunginThe therapeutic efficacy of Micafungin can be increased when used in combination with Benidipine.Approved, Investigational
MiconazoleThe therapeutic efficacy of Miconazole can be increased when used in combination with Benidipine.Approved, Investigational, Vet Approved
MifepristoneThe serum concentration of Benidipine can be increased when it is combined with Mifepristone.Approved, Investigational
MiltefosineThe therapeutic efficacy of Miltefosine can be increased when used in combination with Benidipine.Approved, Investigational
MitotaneThe serum concentration of Benidipine can be decreased when it is combined with Mitotane.Approved
MonensinThe therapeutic efficacy of Monensin can be increased when used in combination with Benidipine.Vet Approved
MyxothiazolThe therapeutic efficacy of Myxothiazol can be increased when used in combination with Benidipine.Experimental
NafcillinThe therapeutic efficacy of Benidipine can be decreased when used in combination with Nafcillin.Approved, Investigational
NaftifineThe therapeutic efficacy of Naftifine can be increased when used in combination with Benidipine.Approved
NatamycinThe therapeutic efficacy of Natamycin can be increased when used in combination with Benidipine.Approved
NefazodoneThe metabolism of Benidipine can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Benidipine can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Benidipine can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of Benidipine can be increased when combined with Nevirapine.Approved
NifuratelThe therapeutic efficacy of Nifuratel can be increased when used in combination with Benidipine.Experimental
Nikkomycin ZThe therapeutic efficacy of Nikkomycin Z can be increased when used in combination with Benidipine.Investigational
NilotinibThe metabolism of Benidipine can be decreased when combined with Nilotinib.Approved, Investigational
NitroprussideBenidipine may increase the hypotensive activities of Nitroprusside.Approved, Investigational
NitroxolineThe therapeutic efficacy of Nitroxoline can be increased when used in combination with Benidipine.Approved
NystatinThe therapeutic efficacy of Nystatin can be increased when used in combination with Benidipine.Approved, Vet Approved
OlaparibThe metabolism of Benidipine can be decreased when combined with Olaparib.Approved
OmoconazoleThe therapeutic efficacy of Omoconazole can be increased when used in combination with Benidipine.Experimental
OsimertinibThe serum concentration of Benidipine can be increased when it is combined with Osimertinib.Approved
OxiconazoleThe therapeutic efficacy of Oxiconazole can be increased when used in combination with Benidipine.Approved
PafuramidineThe therapeutic efficacy of Pafuramidine can be increased when used in combination with Benidipine.Investigational
PalbociclibThe serum concentration of Benidipine can be increased when it is combined with Palbociclib.Approved, Investigational
PentamidineThe therapeutic efficacy of Pentamidine can be increased when used in combination with Benidipine.Approved, Investigational
PentobarbitalThe metabolism of Benidipine can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PhenobarbitalThe metabolism of Benidipine can be increased when combined with Phenobarbital.Approved, Investigational
PhenytoinThe metabolism of Benidipine can be increased when combined with Phenytoin.Approved, Vet Approved
PitolisantThe serum concentration of Benidipine can be decreased when it is combined with Pitolisant.Approved, Investigational
PosaconazoleThe metabolism of Benidipine can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrazosinThe risk or severity of hypotension can be increased when Prazosin is combined with Benidipine.Approved
PrimidoneThe metabolism of Benidipine can be increased when combined with Primidone.Approved, Vet Approved
PyrrolnitrinThe therapeutic efficacy of Pyrrolnitrin can be increased when used in combination with Benidipine.Experimental
RadicicolThe therapeutic efficacy of Radicicol can be increased when used in combination with Benidipine.Experimental
RanolazineThe serum concentration of Benidipine can be increased when it is combined with Ranolazine.Approved, Investigational
RifabutinThe risk or severity of hypotension can be increased when Rifabutin is combined with Benidipine.Approved, Investigational
RifampicinThe risk or severity of hypotension can be increased when Rifampicin is combined with Benidipine.Approved
RifapentineThe risk or severity of hypotension can be increased when Rifapentine is combined with Benidipine.Approved, Investigational
RifaximinThe risk or severity of hypotension can be increased when Rifaximin is combined with Benidipine.Approved, Investigational
RucaparibThe metabolism of Benidipine can be decreased when combined with Rucaparib.Approved, Investigational
Salicylhydroxamic AcidThe therapeutic efficacy of Salicylhydroxamic Acid can be increased when used in combination with Benidipine.Experimental
Salicylic acidThe therapeutic efficacy of Salicylic acid can be increased when used in combination with Benidipine.Approved, Investigational, Vet Approved
SaquinavirThe metabolism of Benidipine can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Benidipine can be decreased when used in combination with Sarilumab.Approved, Investigational
SecobarbitalThe metabolism of Benidipine can be increased when combined with Secobarbital.Approved, Vet Approved
SertaconazoleThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Benidipine.Approved, Investigational
SildenafilThe metabolism of Benidipine can be decreased when combined with Sildenafil.Approved, Investigational
SilodosinThe risk or severity of hypotension can be increased when Silodosin is combined with Benidipine.Approved
SiltuximabThe serum concentration of Benidipine can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of Benidipine can be increased when it is combined with Simeprevir.Approved
SinefunginThe therapeutic efficacy of Sinefungin can be increased when used in combination with Benidipine.Experimental
SirolimusThe therapeutic efficacy of Sirolimus can be increased when used in combination with Benidipine.Approved, Investigational
St. John's WortThe serum concentration of Benidipine can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Benidipine can be increased when it is combined with Stiripentol.Approved
SulconazoleThe therapeutic efficacy of Sulconazole can be increased when used in combination with Benidipine.Approved
SulfisoxazoleThe metabolism of Benidipine can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TamsulosinThe risk or severity of hypotension can be increased when Tamsulosin is combined with Benidipine.Approved, Investigational
TavaboroleThe therapeutic efficacy of Tavaborole can be increased when used in combination with Benidipine.Approved, Investigational
TelaprevirThe metabolism of Benidipine can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Benidipine can be decreased when combined with Telithromycin.Approved
TerazosinThe risk or severity of hypotension can be increased when Terazosin is combined with Benidipine.Approved
TerbinafineThe therapeutic efficacy of Terbinafine can be increased when used in combination with Benidipine.Approved, Investigational, Vet Approved
TerconazoleThe therapeutic efficacy of Terconazole can be increased when used in combination with Benidipine.Approved
ThiamylalThe metabolism of Benidipine can be increased when combined with Thiamylal.Approved, Vet Approved
ThiopentalThe metabolism of Benidipine can be increased when combined with Thiopental.Approved, Vet Approved
ThymolThe therapeutic efficacy of Thymol can be increased when used in combination with Benidipine.Approved
TiclopidineThe metabolism of Benidipine can be decreased when combined with Ticlopidine.Approved
TioconazoleThe therapeutic efficacy of Tioconazole can be increased when used in combination with Benidipine.Approved
TocilizumabThe serum concentration of Benidipine can be decreased when it is combined with Tocilizumab.Approved
TolciclateThe therapeutic efficacy of Tolciclate can be increased when used in combination with Benidipine.Experimental
TolnaftateThe therapeutic efficacy of Tolnaftate can be increased when used in combination with Benidipine.Approved, Investigational, Vet Approved
TrimazosinThe risk or severity of hypotension can be increased when Trimazosin is combined with Benidipine.Experimental
TrimetrexateThe therapeutic efficacy of Trimetrexate can be increased when used in combination with Benidipine.Approved, Investigational
UrapidilThe risk or severity of hypotension can be increased when Urapidil is combined with Benidipine.Investigational
VemurafenibThe serum concentration of Benidipine can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Benidipine can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Benidipine can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Benidipine can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Benidipine can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. Terada K, Nakao K, Okabe K, Kitamura K, Kuriyama H: Action of the 1,4-dihydropyridine derivative, KW-3049, on the smooth muscle membrane of the rabbit mesenteric artery. Br J Pharmacol. 1987 Nov;92(3):615-25. [PubMed:3427272]
  2. Yao K, Nagashima K, Miki H: Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci. 2006 Apr;100(4):243-61. Epub 2006 Mar 25. [PubMed:16565579]
  3. Yoon YJ, Kim KB, Kim H, Seo KA, Kim HS, Cha IJ, Kim EY, Liu KH, Shin JG: Characterization of benidipine and its enantiomers' metabolism by human liver cytochrome P450 enzymes. Drug Metab Dispos. 2007 Sep;35(9):1518-24. doi: 10.1124/dmd.106.013607. Epub 2007 May 30. [PubMed:17537876]
  4. IJBCP [Link]
  5. Springer [Link]
External Links
PubChem Compound
656668
PubChem Substance
310265135
ChemSpider
571013
ChEMBL
CHEMBL2105555
Wikipedia
Benidipine
ATC Codes
C08CA15 — Benidipine
MSDS
Download (291 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Not Yet RecruitingTreatmentChronic Kidney Disease (CKD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)>193ºC'MSDS'
water solubility<1 mg/ml'MSDS'
logP3.79Yao K, et al. J Pharmacol Sci. (2006)
pKa7.34US 4448964
Predicted Properties
PropertyValueSource
Water Solubility0.00243 mg/mLALOGPS
logP4.28ALOGPS
logP4.02ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)19.47ChemAxon
pKa (Strongest Basic)7.89ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area111.01 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity141 m3·mol-1ChemAxon
Polarizability53.53 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-benzylpiperidines. These are heterocyclic Compounds containing a piperidine ring conjugated to a benzyl group through one nitrogen ring atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Benzylpiperidines
Direct Parent
N-benzylpiperidines
Alternative Parents
Dihydropyridinecarboxylic acids and derivatives / Nitrobenzenes / Phenylmethylamines / Benzylamines / Nitroaromatic compounds / Aralkylamines / Dicarboxylic acids and derivatives / Vinylogous amides / Methyl esters / Enoate esters
show 12 more
Substituents
N-benzylpiperidine / Nitrobenzene / Dihydropyridinecarboxylic acid derivative / Phenylmethylamine / Nitroaromatic compound / Benzylamine / Dihydropyridine / Aralkylamine / Monocyclic benzene moiety / Benzenoid
show 32 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...

Components:
References
  1. Yao K, Nagashima K, Miki H: Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci. 2006 Apr;100(4):243-61. Epub 2006 Mar 25. [PubMed:16565579]
  2. IJBCP [Link]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1B
Uniprot ID
Q00975
Uniprot Name
Voltage-dependent N-type calcium channel subunit alpha-1B
Molecular Weight
262493.84 Da
References
  1. Yao K, Nagashima K, Miki H: Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci. 2006 Apr;100(4):243-61. Epub 2006 Mar 25. [PubMed:16565579]
  2. IJBCP [Link]
Kind
Protein group
Organism
Homo sapiens
Pharmacological action
Yes
Actions
Antagonist
General Function
Scaffold protein binding
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...

Components:
References
  1. Yao K, Nagashima K, Miki H: Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci. 2006 Apr;100(4):243-61. Epub 2006 Mar 25. [PubMed:16565579]
  2. IJBCP [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Yao K, Nagashima K, Miki H: Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci. 2006 Apr;100(4):243-61. Epub 2006 Mar 25. [PubMed:16565579]
  2. Yoon YJ, Kim KB, Kim H, Seo KA, Kim HS, Cha IJ, Kim EY, Liu KH, Shin JG: Characterization of benidipine and its enantiomers' metabolism by human liver cytochrome P450 enzymes. Drug Metab Dispos. 2007 Sep;35(9):1518-24. doi: 10.1124/dmd.106.013607. Epub 2007 May 30. [PubMed:17537876]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Yao K, Nagashima K, Miki H: Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci. 2006 Apr;100(4):243-61. Epub 2006 Mar 25. [PubMed:16565579]
  2. Yoon YJ, Kim KB, Kim H, Seo KA, Kim HS, Cha IJ, Kim EY, Liu KH, Shin JG: Characterization of benidipine and its enantiomers' metabolism by human liver cytochrome P450 enzymes. Drug Metab Dispos. 2007 Sep;35(9):1518-24. doi: 10.1124/dmd.106.013607. Epub 2007 May 30. [PubMed:17537876]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Yoon YJ, Kim KB, Kim H, Seo KA, Kim HS, Cha IJ, Kim EY, Liu KH, Shin JG: Characterization of benidipine and its enantiomers' metabolism by human liver cytochrome P450 enzymes. Drug Metab Dispos. 2007 Sep;35(9):1518-24. doi: 10.1124/dmd.106.013607. Epub 2007 May 30. [PubMed:17537876]

Drug created on October 23, 2015 10:16 / Updated on March 02, 2018 05:17