nimodipine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
calcium channel blockers, nifedipine derivatives 1937 66085-59-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nimodipine
  • nemotan
  • nymalize
A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.
  • Molecular weight: 418.45
  • Formula: C21H26N2O7
  • CLOGP: 4
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 1
  • TPSA: 117
  • ALOGS: -4.54
  • ROTB: 10
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.30 g O
50 mg P

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) 14.34 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 16 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.10 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 15 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) 1.30 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.890 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.296 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 48.084 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 111.173 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 1.540 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 2.550 % High 1
herg hERG pIC50 4.855 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 149.279 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 293.765 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 1.450 % High 1
kinase-safety-class ACVR2B,AKT2,AURKA,AXL,BRAF,BTK,CAMK2B,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,PIK3CG,PIM2,PRKDC,STK33,TEK,TTK,ZAP70 40
kinase-selectivity-class AXL,BRAF,CDK9,DDR1,GRK2,MAPK7,PIK3CD,STK33,TEK 9
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.606 High 1
mh-clint Mouse hepatocyte intrinsic clearance 149.279 High 1
mppb Mouse plasma protein binding (% unbound) 0.840 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 7.482 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 High 1
pppb Pig plasma protein binding (% unbound) 1.700 % High 1
rh-clint Rat hepatocyte intrinsic clearance 239.332 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 17.320 % High 1
rppb Rat plasma protein binding (% unbound) 1.460 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 13.213 uM High 1

Approvals:

DateAgencyCompanyOrphan
Dec. 28, 1988 FDA

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
Cholestasis 94.17 40.26 29 1036 36270 90591112
Patent ductus arteriosus 81.07 40.26 17 1048 4552 90622830
Reversible cerebral vasoconstriction syndrome 76.94 40.26 16 1049 4114 90623268
Subarachnoid haemorrhage 76.08 40.26 21 1044 17883 90609499
Vasoplegia syndrome 52.97 40.26 11 1054 2803 90624579
Abortion missed 50.69 40.26 10 1055 1972 90625410
Hypertransaminasaemia 46.77 40.26 14 1051 15811 90611571
Posterior reversible encephalopathy syndrome 46.05 40.26 15 1050 22324 90605058
Cerebral vasoconstriction 42.55 40.26 8 1057 1226 90626156
Premature baby 40.44 40.26 14 1051 25063 90602319

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
Cerebral ischaemia 83.21 58.78 20 697 6939 42613679
Brain injury 81.32 58.78 20 697 7635 42612983
Intensive care unit acquired weakness 64.02 58.78 12 705 1266 42619352
Sinus bradycardia 63.79 58.78 19 698 14834 42605784
Alcohol abuse 60.76 58.78 14 703 4035 42616583

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
Subarachnoid haemorrhage 107.35 33.86 33 1756 29669 110557841
Cerebral ischaemia 91.76 33.86 24 1765 12080 110575430
Reversible cerebral vasoconstriction syndrome 85.83 33.86 19 1770 4742 110582768
Mixed liver injury 77.54 33.86 21 1768 12058 110575452
Vasoplegia syndrome 72.65 33.86 17 1772 5422 110582088
Brain injury 70.71 33.86 20 1769 13456 110574054
Cholestasis 68.67 33.86 29 1760 64489 110523021
Alcohol abuse 63.70 33.86 15 1774 4914 110582596
Posterior reversible encephalopathy syndrome 59.92 33.86 22 1767 33839 110553671
Thunderclap headache 59.79 33.86 10 1779 568 110586942
Intensive care unit acquired weakness 57.09 33.86 12 1777 2347 110585163
Cerebral vasoconstriction 56.33 33.86 11 1778 1490 110586020
Cardiogenic shock 55.16 33.86 24 1765 57314 110530196
Sinus bradycardia 51.58 33.86 19 1770 29464 110558046
Abortion missed 50.02 33.86 10 1779 1527 110585983
Polyneuropathy 46.48 33.86 18 1771 31994 110555516
Hypotension 45.92 33.86 49 1740 523800 110063710
Behaviour disorder 40.30 33.86 12 1777 9635 110577875
Lactic acidosis 38.68 33.86 22 1767 92789 110494721
Hyperlactacidaemia 37.65 33.86 11 1778 8275 110579235
Alcohol use disorder 37.27 33.86 5 1784 61 110587449
Cognitive disorder 37.16 33.86 21 1768 87490 110500020
Hypertransaminasaemia 36.49 33.86 14 1775 24241 110563269
Nervous system disorder 36.20 33.86 15 1774 31706 110555804

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C08CA06 CARDIOVASCULAR SYSTEM
CALCIUM CHANNEL BLOCKERS
SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS
Dihydropyridine derivatives
FDA CS M0006414 Dihydropyridines
FDA MoA N0000000069 Calcium Channel Antagonists
FDA EPC N0000175421 Dihydropyridine Calcium Channel Blocker
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:35476 antipsychotic agent
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35610 antineoplastic agent
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:50247 antidote

Related Drugs by ATC class:

C08CA Dihydropyridine derivatives 17 drugs
amlodipinebarnidipinebenidipinecelecoxibcilnidipineclevidipinefelodipineisradipinelacidipinelercanidipinelevamlodipinemanidipine show all 17 →

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

DiseaseRelationSNOMED_IDDOID
Subarachnoid intracranial hemorrhage indication 21454007
nerve regeneration after iatrogenic nerve injury off-label use 57182000
Essential tremor off-label use 609558009 DOID:4990
Low blood pressure contraindication 45007003
Chronic idiopathic constipation contraindication 82934008
Disease of liver contraindication 235856003 DOID:409




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 2.09 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
6MG/ML NYMALIZE AZURITY N203340 April 8, 2020 RX SOLUTION ORAL 10342787 April 16, 2038 A METHOD FOR THE IMPROVEMENT OF NEUROLOGICAL OUTCOME BY REDUCING THE INCIDENCE AND SEVERITY OF ISCHEMIC DEFICITS IN ADULT PATIENTS WITH SUBARACHNOID HEMORRHAGE (SAH) FROM RUPTURED INTRACRANIAL BERRY ANEURYSMS
6MG/ML NYMALIZE AZURITY N203340 April 8, 2020 RX SOLUTION ORAL 10576070 April 16, 2038 A METHOD FOR THE IMPROVEMENT OF NEUROLOGICAL OUTCOME BY REDUCING THE INCIDENCE AND SEVERITY OF ISCHEMIC DEFICITS IN ADULT PATIENTS WITH SUBARACHNOID HEMORRHAGE (SAH) FROM RUPTURED INTRACRANIAL BERRY ANEURYSMS
6MG/ML NYMALIZE AZURITY N203340 April 8, 2020 RX SOLUTION ORAL 11207306 April 16, 2038 A METHOD FOR THE IMPROVEMENT OF NEUROLOGICAL OUTCOME BY REDUCING THE INCIDENCE AND SEVERITY OF ISCHEMIC DEFICITS IN ADULT PATIENTS WITH SUBARACHNOID HEMORRHAGE (SAH) FROM RUPTURED INTRACRANIAL BERRY ANEURYSMS
6MG/ML NYMALIZE AZURITY N203340 April 8, 2020 RX SOLUTION ORAL 11413277 April 16, 2038 A METHOD FOR THE IMPROVEMENT OF NEUROLOGICAL OUTCOME BY REDUCING THE INCIDENCE AND SEVERITY OF ISCHEMIC DEFICITS IN ADULT PATIENTS WITH SUBARACHNOID HEMORRHAGE (SAH) FROM RUPTURED INTRACRANIAL BERRY ANEURYSMS
6MG/ML NYMALIZE AZURITY N203340 April 8, 2020 RX SOLUTION ORAL 12186308 April 16, 2038 A METHOD FOR THE IMPROVEMENT OF NEUROLOGICAL OUTCOME BY REDUCING THE INCIDENCE AND SEVERITY OF ISCHEMIC DEFICITS IN ADULT PATIENTS WITH SUBARACHNOID HEMORRHAGE (SAH) FROM RUPTURED INTRACRANIAL BERRY ANEURYSMS

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 BLOCKER UNKNOWN CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel BLOCKER UNKNOWN CHEMBL
Cytochrome P450 3A4 Enzyme Ki 6.12 WOMBAT-PK
Adenosine receptor A3 GPCR Ki 5.07 WOMBAT-PK
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor EC50 6.41 CHEMBL
Voltage-dependent calcium channel gamma-1 subunit Ion channel WOMBAT-PK
Mineralocorticoid receptor Nuclear hormone receptor ANTAGONIST IC50 6.80 IUPHAR
ATP-binding cassette sub-family G member 2 Transporter IC50 4.86 CHEMBL
Cytochrome P450 2C9 Enzyme IC50 6 DRUG MATRIX
Voltage-dependent T-type calcium channel subunit alpha-1H Ion channel Ki 5.25 WOMBAT-PK
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Enzyme IC50 5.70 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1S Ion channel GATING INHIBITOR IC50 6 IUPHAR
Cytochrome P450 2C19 Enzyme IC50 5.40 DRUG MATRIX
cAMP-specific 3',5'-cyclic phosphodiesterase 4D Enzyme IC50 5.15 CHEMBL
Bile acid receptor Nuclear hormone receptor IC50 5.05 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1F Ion channel GATING INHIBITOR IC50 6 IUPHAR
Sodium/nucleoside cotransporter 1 Transporter Ki 6.36 DRUG MATRIX
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C Enzyme IC50 5.91 CHEMBL
Cannabinoid receptor 1 GPCR Ki 5.86 DRUG MATRIX
Adenosine receptor A1 GPCR Ki 4.70 CHEMBL
Adenosine receptor A2a GPCR Ki 4.35 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel GATING INHIBITOR IC50 6.80 IUPHAR
Voltage-dependent L-type calcium channel subunit alpha-1D Ion channel GATING INHIBITOR IC50 6.60 IUPHAR

External reference:

IDSource
4019390 VUID
N0000147543 NUI
D00438 KEGG_DRUG
4019390 VANDF
C0028094 UMLSCUI
CHEBI:7575 CHEBI
CHEMBL1428 ChEMBL_ID
D009553 MESH_DESCRIPTOR_UI
DB00393 DRUGBANK_ID
4497 PUBCHEM_CID
2523 IUPHAR_LIGAND_ID
4528 INN_ID
57WA9QZ5WH UNII
1423768 RXNORM
109672 MMSL
203915 MMSL
5177 MMSL
d00318 MMSL
000713 NDDF
387502003 SNOMEDCT_US
87285001 SNOMEDCT_US
6U9 PDB_CHEM_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
nimodipine HUMAN PRESCRIPTION DRUG LABEL 1 23155-512 CAPSULE, LIQUID FILLED 30 mg ORAL ANDA 13 sections
Nymalize HUMAN PRESCRIPTION DRUG LABEL 1 24338-230 SOLUTION 30 mg ORAL NDA 26 sections
Nymalize HUMAN PRESCRIPTION DRUG LABEL 1 24338-260 SOLUTION 60 mg ORAL NDA 26 sections
Nimodipine HUMAN PRESCRIPTION DRUG LABEL 1 31722-039 SOLUTION 60 mg ORAL ANDA 24 sections
Nimodipine HUMAN PRESCRIPTION DRUG LABEL 1 69452-209 CAPSULE, LIQUID FILLED 30 mg ORAL ANDA 23 sections