nitrendipine ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
calcium channel blockers, nifedipine derivatives 1947 39562-70-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nitrendipine
  • nitrendipin
  • nitrepin
A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.
  • Molecular weight: 360.37
  • Formula: C18H20N2O6
  • CLOGP: 3.73
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 1
  • TPSA: 107.77
  • ALOGS: -4.41
  • ROTB: 7

Drug dosage:

DoseUnitRoute
20 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.00 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.92 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 16.50 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 6.10 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 25 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.02 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 8.20 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.941 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.239 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 51.168 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 119.124 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.980 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 1.620 % High 1
herg hERG pIC50 4.959 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 73.961 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 252.348 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.990 % High 1
kinase-safety-class ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,GRK2,GSK3B,ITK,JAK2,JAK3,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MET,NTRK2,PDK1,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIM2,PRKDC,STK33,TEK,TTK,ZAP70 37
kinase-selectivity-class AXL,BRAF,CDK9,GRK2,MAPK7,PDK4,STK33,TEK 8
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.104 High 1
mh-clint Mouse hepatocyte intrinsic clearance 80.724 High 1
mppb Mouse plasma protein binding (% unbound) 0.530 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 5.610 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 Moderate 0.72
pppb Pig plasma protein binding (% unbound) 1.620 % High 1
rh-clint Rat hepatocyte intrinsic clearance 193.642 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 17.410 % High 1
rppb Rat plasma protein binding (% unbound) 0.690 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 22.182 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 1, 1985 YEAR INTRODUCED

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Antinuclear antibody negative 102.89 35.16 16 3000 270 90625161
Fall 94.74 35.16 97 2919 481713 90143718
Coombs positive haemolytic anaemia 94.28 35.16 16 3000 474 90624957
Product prescribing error 79.97 35.16 32 2984 30113 90595318
Herpes simplex reactivation 76.45 35.16 15 3001 1004 90624427
General physical health deterioration 74.22 35.16 74 2942 355041 90270390
Gastritis haemorrhagic 73.50 35.16 16 3000 1784 90623647
Antiphospholipid syndrome 69.78 35.16 16 3000 2258 90623173
Complex regional pain syndrome 67.29 35.16 16 3000 2643 90622788
Hypertensive crisis 61.86 35.16 23 2993 17761 90607670
Anxiety disorder 57.51 35.16 16 3000 4906 90620525
Lymphopenia 56.23 35.16 23 2993 22858 90602573
Hyperlipidaemia 52.80 35.16 22 2994 22894 90602537
Leukopenia 50.63 35.16 35 2981 100675 90524756
Erysipelas 47.90 35.16 16 3000 9036 90616395
Torticollis 47.49 35.16 12 3004 2546 90622885
Hypertensive angiopathy 47.31 35.16 7 3009 83 90625348
Pleuritic pain 45.63 35.16 16 3000 10445 90614986
Premature baby 44.43 35.16 20 2996 25057 90600374
Pancreatitis acute 39.71 35.16 20 2996 32095 90593336
Bradycardia 39.47 35.16 28 2988 83819 90541612
Peritonitis 39.04 35.16 17 2999 19688 90605743
Hypertension 37.84 35.16 60 2956 457472 90167959
Aspergillus infection 37.63 35.16 14 3002 10809 90614622
Pneumocystis jirovecii pneumonia 37.53 35.16 17 2999 21599 90603832
Humerus fracture 35.28 35.16 13 3003 9772 90615659

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Rectal prolapse 106.10 33.33 21 3705 547 42617062
Renal cyst haemorrhage 102.02 33.33 21 3705 669 42616940
Abdominal wall haemorrhage 83.86 33.33 17 3709 501 42617108
Vena cava injury 78.24 33.33 15 3711 329 42617280
Carotid arteriosclerosis 76.59 33.33 21 3705 2311 42615298
SARS-CoV-2 antibody test positive 75.84 33.33 15 3711 389 42617220
Delayed graft function 74.05 33.33 21 3705 2614 42614995
Vascular anastomotic haemorrhage 73.38 33.33 14 3712 299 42617310
Spinal osteoarthritis 66.71 33.33 26 3700 8660 42608949
Mean cell volume increased 65.81 33.33 21 3705 3902 42613707
Product prescribing error 65.73 33.33 36 3690 26076 42591533
Left ventricular hypertrophy 64.94 33.33 26 3700 9293 42608316
Diverticulum intestinal 64.23 33.33 22 3704 5091 42612518
Vascular compression 64.19 33.33 13 3713 381 42617228
Aortic dilatation 64.07 33.33 17 3709 1652 42615957
Hyperparathyroidism secondary 62.41 33.33 17 3709 1825 42615784
Hepatosplenomegaly 62.26 33.33 21 3705 4639 42612970
Dizziness 61.52 33.33 91 3635 249163 42368446
Intraductal papillary mucinous neoplasm 61.34 33.33 13 3713 478 42617131
Aortic arteriosclerosis 60.32 33.33 21 3705 5099 42612510
Actinic keratosis 60.10 33.33 21 3705 5155 42612454
Renal artery stenosis 58.55 33.33 17 3709 2300 42615309
Perineal cyst 57.60 33.33 11 3715 236 42617373
Syncope 57.33 33.33 56 3670 99350 42518259
Gastroduodenal ulcer 56.47 33.33 13 3713 702 42616907
Intervertebral disc space narrowing 55.30 33.33 14 3712 1131 42616478
Blood 25-hydroxycholecalciferol decreased 54 33.33 11 3715 332 42617277
Hemiparaesthesia 53.57 33.33 10 3716 189 42617420
Spinal stenosis 52.12 33.33 20 3706 6386 42611223
General physical health deterioration 48.92 33.33 63 3663 151183 42466426
Restless legs syndrome 47.48 33.33 21 3705 9593 42608016
Benign prostatic hyperplasia 44.77 33.33 26 3700 21026 42596583
Glycosylated haemoglobin increased 44.51 33.33 22 3704 12902 42604707
Swelling of eyelid 42.42 33.33 13 3713 2115 42615494
Squamous cell carcinoma of skin 41.86 33.33 21 3705 12705 42604904
Aortic valve incompetence 41.26 33.33 17 3709 6531 42611078
Vitamin D decreased 39.99 33.33 15 3711 4500 42613109
Vertigo 37.60 33.33 28 3698 34319 42583290
Complications of transplanted kidney 37.52 33.33 15 3711 5335 42612274
Swelling 37.49 33.33 34 3692 54851 42562758
Activated partial thromboplastin time prolonged 37.46 33.33 21 3705 15882 42601727
Blood potassium increased 37.06 33.33 22 3704 18514 42599095
Tongue biting 36.67 33.33 10 3716 1077 42616532
Haemorrhoids 36.04 33.33 21 3705 17076 42600533
Pulmonary hypertension 34.61 33.33 23 3703 23546 42594063
Hepatic steatosis 34.10 33.33 22 3704 21426 42596183
Osteochondrosis 34.04 33.33 10 3716 1408 42616201
Oedema peripheral 33.88 33.33 50 3676 136026 42481583

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Product prescribing error 151.04 31.85 68 6060 51263 110531908
General physical health deterioration 119.97 31.85 132 5996 425163 110158008
Renal cyst haemorrhage 109.50 31.85 21 6107 740 110582431
Syncope 96.74 31.85 84 6044 202452 110380719
Delayed graft function 96.56 31.85 26 6102 4231 110578940
Dizziness 88.89 31.85 147 5981 698046 109885125
Abdominal wall haemorrhage 85.23 31.85 17 6111 736 110582435
Vena cava injury 84.72 31.85 15 6113 337 110582834
Rectal prolapse 84.10 31.85 21 6107 2542 110580629
SARS-CoV-2 antibody test positive 82.25 31.85 15 6113 400 110582771
Carotid arteriosclerosis 80.43 31.85 21 6107 3036 110580135
Vascular anastomotic haemorrhage 79.74 31.85 14 6114 299 110582872
Bradycardia 79.31 31.85 67 6061 155450 110427721
Renal artery stenosis 71.71 31.85 20 6108 3706 110579465
Left ventricular hypertrophy 71.13 31.85 27 6101 13217 110569954
Complications of transplanted kidney 69.94 31.85 23 6105 7419 110575752
Tongue biting 66.88 31.85 18 6110 2921 110580250
Aortic dilatation 66.74 31.85 17 6111 2229 110580942
Fall 64.82 31.85 118 6010 603364 109979807
Hepatosplenomegaly 63.49 31.85 21 6107 6898 110576273
Actinic keratosis 63.21 31.85 21 6107 6992 110576179
Perineal cyst 62.74 31.85 11 6117 233 110582938
Vascular compression 61.22 31.85 13 6115 768 110582403
Hyperparathyroidism secondary 60.23 31.85 17 6111 3287 110579884
Intraductal papillary mucinous neoplasm 59.99 31.85 13 6115 846 110582325
Mean cell volume increased 59.67 31.85 21 6107 8309 110574862
Benign prostatic hyperplasia 59.50 31.85 26 6102 18208 110564963
Gastroduodenal ulcer 58.40 31.85 13 6115 958 110582213
Blood 25-hydroxycholecalciferol decreased 55.40 31.85 11 6117 465 110582706
Intervertebral disc space narrowing 54.61 31.85 14 6114 1882 110581289
Aortic arteriosclerosis 54.09 31.85 21 6107 10917 110572254
Diverticulum intestinal 52.69 31.85 21 6107 11698 110571473
Hemiparaesthesia 50.95 31.85 10 6118 398 110582773
Spinal osteoarthritis 50.75 31.85 24 6104 20159 110563012
Squamous cell carcinoma of skin 44.93 31.85 21 6107 17182 110565989
Glycosylated haemoglobin increased 44.27 31.85 23 6105 23596 110559575
Hypertensive angiopathy 42.73 31.85 7 6121 97 110583074
Presyncope 42.52 31.85 29 6099 48858 110534313
Hypertensive crisis 40.78 31.85 22 6106 24350 110558821
Antinuclear antibody negative 40.03 31.85 7 6121 146 110583025
Spinal stenosis 39.91 31.85 20 6108 19036 110564135
Activated partial thromboplastin time prolonged 39.70 31.85 21 6107 22347 110560824
Torticollis 38.69 31.85 12 6116 3209 110579962
Restless legs syndrome 37.80 31.85 21 6107 24605 110558566
Hypertension 37.12 31.85 85 6043 509999 110073172
Dysuria 37.09 31.85 29 6099 60202 110522969
Blood potassium increased 34.44 31.85 22 6106 33227 110549944
Swelling of eyelid 33.70 31.85 13 6115 6640 110576531
Haematoma 33.53 31.85 27 6101 58449 110524722
Postrenal failure 32.89 31.85 8 6120 868 110582303
Arteriosclerosis 32.33 31.85 19 6109 24748 110558423
Vitamin D decreased 32.17 31.85 15 6113 12200 110570971
Anaemia 32.16 31.85 84 6044 547002 110036169
Abdominal pain lower 32.14 31.85 22 6106 37261 110545910

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C08CA08 CARDIOVASCULAR SYSTEM
CALCIUM CHANNEL BLOCKERS
SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS
Dihydropyridine derivatives
ATC C09BB06 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ACE INHIBITORS, COMBINATIONS
ACE inhibitors and calcium channel blockers
MeSH PA D000077264 Calcium-Regulating Hormones and Agents
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002121 Calcium Channel Blockers
MeSH PA D002317 Cardiovascular Agents
MeSH PA D014665 Vasodilator Agents
MeSH PA D049990 Membrane Transport Modulators
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35620 vasodilator agent
CHEBI has role CHEBI:35674 antihypertensive agent
CHEBI has role CHEBI:38215 calcium channel blocker
CHEBI has role CHEBI:176497 geroprotector

Related Drugs by ATC class:

C08CA Dihydropyridine derivatives 17 drugs
C09BB ACE inhibitors and calcium channel blockers 13 drugs

Drug Use | Suggest Off label Use Form| |View source of the data|

None




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 2.37 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Voltage-dependent L-type calcium channel subunit alpha-1D Ion channel GATING INHIBITOR IC50 8.40 IUPHAR IUPHAR
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel BLOCKER Ki 9.60 CHEMBL SCIENTIFIC LITERATURE
Intermediate conductance calcium-activated potassium channel protein 4 Ion channel BLOCKER IC50 7.60 IUPHAR
Voltage-dependent calcium channel gamma-1 subunit Ion channel WOMBAT-PK
Transthyretin Secreted IC50 5.92 WOMBAT-PK
ATP-binding cassette sub-family G member 2 Transporter IC50 4.68 CHEMBL
Cytochrome P450 2C9 Enzyme IC50 6.52 DRUG MATRIX
Voltage-dependent T-type calcium channel subunit alpha-1H Ion channel IC50 5.06 WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1F Ion channel GATING INHIBITOR IC50 6 IUPHAR
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C Enzyme IC50 5.73 CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III) Ion channel IC50 4.44 CHEMBL
Cytochrome P450 2C19 Enzyme IC50 5.52 DRUG MATRIX
Adenosine receptor A3 GPCR Ki 5.08 WOMBAT-PK
Adenosine receptor A1 GPCR Ki 5.05 CHEMBL
Adenosine receptor A2a GPCR Ki 4.64 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel GATING INHIBITOR IC50 6 IUPHAR
Voltage-dependent L-type calcium channel subunit alpha-1S Ion channel GATING INHIBITOR IC50 6 IUPHAR
Platelet-activating factor receptor GPCR Ki 4.13 CHEMBL

External reference:

IDSource
N0000167238 NUI
D00629 KEGG_DRUG
C0028127 UMLSCUI
CHEBI:7582 CHEBI
CHEMBL475534 ChEMBL_ID
DB01054 DRUGBANK_ID
D009568 MESH_DESCRIPTOR_UI
4507 PUBCHEM_CID
2334 IUPHAR_LIGAND_ID
4739 INN_ID
9B627AW319 UNII
7441 RXNORM
005383 NDDF
444757009 SNOMEDCT_US
9B627AW319 INXIGHT DRUGS

Pharmaceutical products:

None