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([C@@H]1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)O[C@@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]

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
AbafunginThe therapeutic efficacy of Abafungin can be increased when used in combination with Benidipine.Investigational
AcepromazineThe risk or severity of hypotension can be increased when Acepromazine is combined with Benidipine.Approved, Vet Approved
AlbaconazoleThe therapeutic efficacy of Albaconazole can be increased when used in combination with Benidipine.Investigational
AlcuroniumBenidipine may increase the neuromuscular blocking activities of Alcuronium.Experimental
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
AmitriptylineThe risk or severity of hypotension can be increased when Amitriptyline is combined with Benidipine.Approved
AmobarbitalThe metabolism of Benidipine can be increased when combined with Amobarbital.Approved, Illicit
AmoxapineThe risk or severity of hypotension can be increased when Amoxapine is combined with Benidipine.Approved
Amphotericin BBenidipine may decrease the nephrotoxic activities of Amphotericin B.Approved, Investigational
AmprenavirThe metabolism of Benidipine can be decreased when combined with Amprenavir.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
AripiprazoleThe risk or severity of hypotension can be increased when Aripiprazole is combined with Benidipine.Approved, Investigational
Aripiprazole lauroxilThe risk or severity of hypotension can be increased when Aripiprazole lauroxil is combined with Benidipine.Approved, Investigational
ArotinololThe risk or severity of hypotension can be increased when Arotinolol is combined with Benidipine.Investigational
AsenapineThe risk or severity of hypotension can be increased when Asenapine is combined with Benidipine.Approved
AtazanavirThe metabolism of Benidipine can be decreased when combined with Atazanavir.Approved, Investigational
AtracuriumBenidipine may increase the neuromuscular blocking activities of Atracurium.Approved, Experimental, Investigational
Atracurium besylateBenidipine may increase the neuromuscular blocking activities of Atracurium besylate.Approved
BarbexacloneThe metabolism of Benidipine can be increased when combined with Barbexaclone.Experimental
BarbitalThe metabolism of Benidipine can be increased when combined with Barbital.Illicit
BevantololThe risk or severity of hypotension can be increased when Bevantolol is combined with Benidipine.Approved
BifonazoleThe therapeutic efficacy of Bifonazole can be increased when used in combination with Benidipine.Approved, Investigational
BisacodylThe therapeutic efficacy of Bisacodyl can be decreased when used in combination with Benidipine.Approved
BisoxatinThe therapeutic efficacy of Bisoxatin can be decreased when used in combination with Benidipine.Approved
BoceprevirThe metabolism of Benidipine can be decreased when combined with Boceprevir.Approved, Withdrawn
BosentanThe serum concentration of Benidipine can be decreased when it is combined with Bosentan.Approved, Investigational
BrexpiprazoleThe risk or severity of hypotension can be increased when Brexpiprazole is combined with Benidipine.Approved, Investigational
BromocriptineThe risk or severity of hypotension can be increased when Bromocriptine is combined with Benidipine.Approved, Investigational
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
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 CarbonateThe therapeutic efficacy of Benidipine can be decreased when used in combination with Calcium Carbonate.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, 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
CarbamazepineThe metabolism of Benidipine can be increased when combined with Carbamazepine.Approved, Investigational
CarboxymethylcelluloseThe therapeutic efficacy of Carboxymethylcellulose can be decreased when used in combination with Benidipine.Approved, Investigational
CarvedilolThe risk or severity of hypotension can be increased when Carvedilol is combined with Benidipine.Approved, Investigational
Castor oilThe therapeutic efficacy of Castor oil can be decreased when used in combination with Benidipine.Approved, Investigational, Nutraceutical, Vet Approved
CeritinibThe serum concentration of Benidipine can be increased when it is combined with Ceritinib.Approved
ChlorpromazineThe risk or severity of hypotension can be increased when Chlorpromazine is combined with Benidipine.Approved, Investigational, Vet Approved
CimetidineThe serum concentration of Benidipine can be increased when it is combined with Cimetidine.Approved, Investigational
CisatracuriumBenidipine may increase the neuromuscular blocking activities of Cisatracurium.Approved
ClarithromycinThe metabolism of Benidipine can be decreased when combined with Clarithromycin.Approved
ClopidogrelThe therapeutic efficacy of Clopidogrel can be decreased when used in combination with Benidipine.Approved
ClotrimazoleThe metabolism of Benidipine can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of hypotension can be increased when Clozapine is combined with Benidipine.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
CrizotinibThe metabolism of Benidipine can be decreased when combined with Crizotinib.Approved
CurcuminThe metabolism of Benidipine can be decreased when combined with Curcumin.Approved, Investigational
CyclosporineThe metabolism of Benidipine can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Benidipine can be decreased when it is combined with Dabrafenib.Approved, Investigational
DanazolThe metabolism of Benidipine can be decreased when combined with Danazol.Approved
DanthronThe therapeutic efficacy of Danthron can be decreased when used in combination with Benidipine.Approved, Investigational, Withdrawn
DapiprazoleThe risk or severity of hypotension can be increased when Dapiprazole is combined with Benidipine.Approved
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
DexamethasoneThe serum concentration of Benidipine can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DihydroergotamineThe risk or severity of hypotension can be increased when Dihydroergotamine is combined with Benidipine.Approved, Investigational
DiltiazemThe metabolism of Benidipine can be decreased when combined with Diltiazem.Approved, Investigational
DocusateThe therapeutic efficacy of Docusate can be decreased when used in combination with Benidipine.Approved
DoxacuriumBenidipine may increase the neuromuscular blocking activities of Doxacurium.Approved
DoxazosinThe risk or severity of hypotension can be increased when Doxazosin is combined with Benidipine.Approved
DoxepinThe risk or severity of hypotension can be increased when Doxepin is combined with Benidipine.Approved, Investigational
DoxycyclineThe metabolism of Benidipine can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe risk or severity of hypotension can be increased when Dronedarone is combined with Benidipine.Approved
DroperidolThe risk or severity of hypotension can be increased when Droperidol is combined with Benidipine.Approved, Vet 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
ErgotamineThe risk or severity of hypotension can be increased when Ergotamine is combined with Benidipine.Approved
ErythromycinThe metabolism of Benidipine can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
EtravirineThe serum concentration of Benidipine can be decreased when it is combined with Etravirine.Approved
FenticonazoleThe therapeutic efficacy of Fenticonazole can be increased when used in combination with Benidipine.Experimental
FluconazoleThe metabolism of Benidipine can be decreased when combined with Fluconazole.Approved, Investigational
FlupentixolThe risk or severity of hypotension can be increased when Flupentixol is combined with Benidipine.Approved, Investigational, Withdrawn
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 serum concentration of Fosphenytoin can be increased when it is combined with Benidipine.Approved, Investigational
Fusidic AcidThe serum concentration of Benidipine can be increased when it is combined with Fusidic Acid.Approved, Investigational
GallamineBenidipine may increase the neuromuscular blocking activities of Gallamine.Experimental
Gallamine TriethiodideBenidipine may increase the neuromuscular blocking activities of Gallamine Triethiodide.Approved
GlycerinThe therapeutic efficacy of Glycerin can be decreased 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
IloperidoneThe risk or severity of hypotension can be increased when Iloperidone is combined with Benidipine.Approved
ImatinibThe metabolism of Benidipine can be decreased when combined with Imatinib.Approved
ImipramineThe risk or severity of hypotension can be increased when Imipramine is combined with Benidipine.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
IsoniazidThe metabolism of Benidipine can be decreased when combined with Isoniazid.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
LactitolThe therapeutic efficacy of Lactitol can be decreased when used in combination with Benidipine.Investigational
LactuloseThe therapeutic efficacy of Lactulose can be decreased when used in combination with Benidipine.Approved
LinaclotideThe therapeutic efficacy of Linaclotide can be decreased when used in combination 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
LubiprostoneThe therapeutic efficacy of Lubiprostone can be decreased when used in combination with Benidipine.Approved, Investigational
LuliconazoleThe serum concentration of Benidipine can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Benidipine can be increased when combined with Lumacaftor.Approved
Magnesium carbonateThe therapeutic efficacy of Magnesium carbonate can be decreased when used in combination with Benidipine.Approved, Investigational
Magnesium citrateThe therapeutic efficacy of Magnesium citrate can be decreased when used in combination with Benidipine.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 peroxideThe therapeutic efficacy of Magnesium peroxide can be decreased when used in combination with Benidipine.Experimental
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
MannitolThe therapeutic efficacy of Mannitol can be decreased when used in combination with Benidipine.Approved, Investigational
MethohexitalThe metabolism of Benidipine can be increased when combined with Methohexital.Approved
MethotrimeprazineThe risk or severity of hypotension can be increased when Methotrimeprazine is combined with Benidipine.Approved, Investigational
Methyl celluloseThe therapeutic efficacy of Methyl cellulose can be decreased when used in combination with Benidipine.Approved
MethylphenobarbitalThe metabolism of Benidipine can be increased when combined with Methylphenobarbital.Approved
MetocurineBenidipine may increase the neuromuscular blocking activities of Metocurine.Approved
Metocurine IodideBenidipine may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Withdrawn
MibefradilThe metabolism of Benidipine can be decreased when combined with Mibefradil.Investigational, Withdrawn
MiconazoleThe metabolism of Benidipine can be decreased when combined with Miconazole.Approved, Investigational, Vet Approved
MifepristoneThe serum concentration of Benidipine can be increased when it is combined with Mifepristone.Approved, Investigational
Mineral oilThe therapeutic efficacy of Mineral oil can be decreased when used in combination with Benidipine.Approved, Vet Approved
MitotaneThe serum concentration of Benidipine can be decreased when it is combined with Mitotane.Approved
MivacuriumBenidipine may increase the neuromuscular blocking activities of Mivacurium.Approved
ModafinilThe serum concentration of Benidipine can be decreased when it is combined with Modafinil.Approved, Investigational
NafcillinThe therapeutic efficacy of Benidipine can be decreased when used in combination with Nafcillin.Approved, Investigational
NaloxoneThe metabolism of Benidipine can be decreased when combined with Naloxone.Approved, Vet Approved
NefazodoneThe risk or severity of hypotension can be increased when Nefazodone is combined with Benidipine.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
NicardipineThe risk or severity of hypotension can be increased when Nicardipine is combined with Benidipine.Approved, Investigational
NicergolineThe risk or severity of hypotension can be increased when Nicergoline is combined with Benidipine.Approved, Investigational
NiguldipineThe risk or severity of hypotension can be increased when Niguldipine is combined with Benidipine.Experimental
NilotinibThe metabolism of Benidipine can be decreased when combined with Nilotinib.Approved, Investigational
NitroprussideBenidipine may increase the hypotensive activities of Nitroprusside.Approved, Investigational
NortriptylineThe risk or severity of hypotension can be increased when Nortriptyline is combined with Benidipine.Approved
OlanzapineThe risk or severity of hypotension can be increased when Olanzapine is combined with Benidipine.Approved, Investigational
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
OxyphenisatinThe therapeutic efficacy of Oxyphenisatin can be decreased when used in combination with Benidipine.Investigational, Withdrawn
PalbociclibThe serum concentration of Benidipine can be increased when it is combined with Palbociclib.Approved, Investigational
PaliperidoneThe risk or severity of hypotension can be increased when Paliperidone is combined with Benidipine.Approved
PancuroniumBenidipine may increase the neuromuscular blocking activities of Pancuronium.Approved
Patent BlueThe therapeutic efficacy of Benidipine can be decreased when used in combination with Patent Blue.Approved
PentaerithritylThe therapeutic efficacy of Pentaerithrityl can be decreased when used in combination with Benidipine.Experimental
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
PhenolphthaleinThe therapeutic efficacy of Phenolphthalein can be decreased when used in combination with Benidipine.Approved, Withdrawn
PhenoxybenzamineThe risk or severity of hypotension can be increased when Phenoxybenzamine is combined with Benidipine.Approved
PhentolamineThe risk or severity of hypotension can be increased when Phentolamine is combined with Benidipine.Approved
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Benidipine.Approved, Vet Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Benidipine.Approved
PipecuroniumBenidipine may increase the neuromuscular blocking activities of Pipecuronium.Approved
PitolisantThe serum concentration of Benidipine can be decreased when it is combined with Pitolisant.Approved, Investigational
PizotifenThe risk or severity of hypotension can be increased when Pizotifen is combined with Benidipine.Approved
Plantago seedThe therapeutic efficacy of Plantago seed can be decreased when used in combination with Benidipine.Approved, Investigational
PlecanatideThe therapeutic efficacy of Plecanatide can be decreased when used in combination with Benidipine.Approved, Investigational
PolycarbophilThe therapeutic efficacy of Polycarbophil can be decreased when used in combination with Benidipine.Approved
Polyethylene glycolThe therapeutic efficacy of Polyethylene glycol can be decreased when used in combination with Benidipine.Approved, Vet Approved
PosaconazoleThe metabolism of Benidipine can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
Potassium acetateThe therapeutic efficacy of Potassium acetate can be decreased when used in combination with Benidipine.Approved, Investigational
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
PromazineThe risk or severity of hypotension can be increased when Promazine is combined with Benidipine.Approved, Vet Approved
PropericiazineThe risk or severity of hypotension can be increased when Propericiazine is combined with Benidipine.Approved, Investigational
PropiomazineThe risk or severity of hypotension can be increased when Propiomazine is combined with Benidipine.Approved
PropiverineThe risk or severity of hypotension can be increased when Propiverine is combined with Benidipine.Approved, Investigational
PrucaloprideThe therapeutic efficacy of Prucalopride can be decreased when used in combination with Benidipine.Approved
QuetiapineThe risk or severity of hypotension can be increased when Quetiapine is combined with Benidipine.Approved
QuinidineThe risk or severity of hypotension can be increased when Quinidine is combined with Benidipine.Approved, Investigational
QuinineThe metabolism of Benidipine can be increased when combined with Quinine.Approved
RapacuroniumBenidipine may increase the neuromuscular blocking activities of Rapacuronium.Withdrawn
RavuconazoleThe therapeutic efficacy of Ravuconazole can be increased when used in combination with Benidipine.Investigational
RifampicinThe metabolism of Benidipine can be increased when combined with Rifampicin.Approved
RifamycinThe metabolism of Benidipine can be increased when combined with Rifamycin.Investigational
RifapentineThe metabolism of Benidipine can be increased when combined with Rifapentine.Approved, Investigational
RifaximinThe metabolism of Benidipine can be increased when combined with Rifaximin.Approved, Investigational
RimexoloneThe metabolism of Benidipine can be increased when combined with Rimexolone.Approved
RisperidoneThe risk or severity of hypotension can be increased when Risperidone is combined with Benidipine.Approved, Investigational
RitonavirThe metabolism of Benidipine can be decreased when combined with Ritonavir.Approved, Investigational
RocuroniumBenidipine may increase the neuromuscular blocking activities of Rocuronium.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
SennosidesThe therapeutic efficacy of Sennosides can be decreased when used in combination with Benidipine.Approved
SertaconazoleThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Benidipine.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
Sodium phosphate, monobasicThe therapeutic efficacy of Sodium phosphate, monobasic can be decreased when used in combination with Benidipine.Approved
Sodium sulfateThe therapeutic efficacy of Sodium sulfate can be decreased when used in combination with Benidipine.Approved, Vet Approved
Sodium tartrateThe therapeutic efficacy of Sodium tartrate can be decreased when used in combination with Benidipine.Approved
SorbitolThe therapeutic efficacy of Sorbitol can be decreased when used in combination with Benidipine.Approved
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
TamsulosinThe risk or severity of hypotension can be increased when Tamsulosin is combined with Benidipine.Approved, Investigational
TegaserodThe therapeutic efficacy of Tegaserod can be decreased when used in combination with Benidipine.Approved, Investigational, Withdrawn
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
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
ThioproperazineThe risk or severity of hypotension can be increased when Thioproperazine is combined with Benidipine.Approved
ThioridazineThe risk or severity of hypotension can be increased when Thioridazine is combined with Benidipine.Approved, Withdrawn
TioconazoleThe therapeutic efficacy of Tioconazole can be increased when used in combination with Benidipine.Approved
TipranavirThe metabolism of Benidipine can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Benidipine can be decreased when it is combined with Tocilizumab.Approved
TolazolineThe risk or severity of hypotension can be increased when Tolazoline is combined with Benidipine.Approved, Vet Approved
TrazodoneThe risk or severity of hypotension can be increased when Trazodone is combined with Benidipine.Approved, Investigational
TrifluoperazineThe risk or severity of hypotension can be increased when Trifluoperazine is combined with Benidipine.Approved, Investigational
TrimazosinThe risk or severity of hypotension can be increased when Trimazosin is combined with Benidipine.Experimental
TrimipramineThe risk or severity of hypotension can be increased when Trimipramine is combined with Benidipine.Approved
TroleandomycinThe metabolism of Benidipine can be decreased when combined with Troleandomycin.Approved
TubocurarineBenidipine may increase the neuromuscular blocking activities of Tubocurarine.Approved
UrapidilThe risk or severity of hypotension can be increased when Urapidil is combined with Benidipine.Investigational
VecuroniumBenidipine may increase the neuromuscular blocking activities of Vecuronium.Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Benidipine.Approved
VerapamilThe risk or severity of hypotension can be increased when Verapamil is combined with Benidipine.Approved
VoriconazoleThe metabolism of Benidipine can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe risk or severity of hypotension can be increased when Ziprasidone is combined with Benidipine.Approved
ZuclopenthixolThe risk or severity of hypotension can be increased when Zuclopenthixol is combined with Benidipine.Approved, Investigational
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]

Drug created on October 23, 2015 10:16 / Updated on August 02, 2018 07:51