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

Stem definitionDrug idCAS RN
1634 10262-69-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • maprotiline
  • maprotiline hydrochloride
  • maprotiline HCl
A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use.
  • Molecular weight: 277.41
  • Formula: C20H23N
  • CLOGP: 4.52
  • LIPINSKI: 0
  • HAC: 1
  • HDO: 1
  • TPSA: 12.03
  • ALOGS: -6.27
  • ROTB: 4
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O
0.10 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 3.13 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 3 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 11.59 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 68 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 45 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 14 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.11 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 51 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.443 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.545 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 21.727 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 27.733 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 3.650 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 14.150 % High 1
herg hERG pIC50 5.506 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 19.999 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 20.749 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 11.250 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT1,AKT2,AKT3,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK2,JAK3,MAP2K6,MAP3K7,MAPK10,MAPK12,MAPK7,MAPKAPK2,MET,NTRK2,PDK2,PDK4,PDPK1,PIM2,PRKDC,SIK2,SIK3,TEK,TGFBR1,TTK 41
kinase-selectivity-class AXL,EIF2AK3,PDK4 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.708 High 1
mh-clint Mouse hepatocyte intrinsic clearance 140.929 High 1
mppb Mouse plasma protein binding (% unbound) 6.500 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 5.023 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) 14.660 % High 1
rh-clint Rat hepatocyte intrinsic clearance 257.632 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 25.130 % High 1
rppb Rat plasma protein binding (% unbound) 9.560 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 979.490 uM High 1

Approvals:

DateAgencyCompanyOrphan
Dec. 1, 1980 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
Aspiration 63.39 37.58 20 1804 15673 90610950
Polydipsia 62.72 37.58 15 1809 4216 90622407
Embolic stroke 58.10 37.58 14 1810 4058 90622565
Mental disorder 56.24 37.58 22 1802 32296 90594327
Respiration abnormal 48.79 37.58 14 1810 7949 90618674
Junctional ectopic tachycardia 44.55 37.58 7 1817 214 90626409
Conjunctivitis 42.33 37.58 17 1807 26689 90599934
Rhabdomyolysis 40.42 37.58 20 1804 51236 90575387
Foramen magnum stenosis 38.20 37.58 6 1818 183 90626440

FDA Adverse Event Reporting System (Male)

None

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
Aspiration 59.71 39.92 19 1101 30514 110557665
Rhabdomyolysis 55.05 39.92 26 1094 120375 110467804
Polydipsia 53.68 39.92 13 1107 7675 110580504
Embolic stroke 52.02 39.92 13 1107 8730 110579449
Respiration abnormal 50.54 39.92 13 1107 9796 110578383
Conjunctivitis 49.86 39.92 17 1103 33775 110554404
Decreased interest 43.14 39.92 10 1110 4898 110583281
Intestinal obstruction 42.33 39.92 17 1103 53210 110534969
Mental disorder 40.12 39.92 15 1105 38776 110549403

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N06AA21 NERVOUS SYSTEM
PSYCHOANALEPTICS
ANTIDEPRESSANTS
Non-selective monoamine reuptake inhibitors
MeSH PA D000928 Antidepressive Agents
MeSH PA D011619 Psychotropic Drugs
MeSH PA D014179 Neurotransmitter Uptake Inhibitors
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018663 Adrenergic Agents
MeSH PA D018687 Antidepressive Agents, Second-Generation
MeSH PA D018759 Adrenergic Uptake Inhibitors
MeSH PA D049990 Membrane Transport Modulators
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:35474 anxiolytic drug
CHEBI has role CHEBI:35476 antipsychotic agent
CHEBI has role CHEBI:35610 antineoplastic agent

Related Drugs by ATC class:

N06AA Non-selective monoamine reuptake inhibitors 20 drugs
amineptineamitriptylineamoxapinebutriptylineclomipraminedesipraminedibenzepindimetacrinedosulepindoxepinimipramineimipramine oxide show all 20 →

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

DiseaseRelationSNOMED_IDDOID
Depressive disorder indication 35489007
Mixed anxiety and depressive disorder indication 231504006
Neuralgia off-label use 16269008
Ocular hypertension contraindication 4210003 DOID:9282
Suicidal thoughts contraindication 6471006
Alcoholism contraindication 7200002
Sinus tachycardia contraindication 11092001
Bipolar disorder contraindication 13746004 DOID:3312
Myocardial infarction contraindication 22298006 DOID:5844
Hyperthyroidism contraindication 34486009 DOID:7998
Conduction disorder of the heart contraindication 44808001
Disorder of cardiovascular system contraindication 49601007 DOID:1287
Seizure disorder contraindication 128613002
Cerebrovascular accident contraindication 230690007
Disease of liver contraindication 235856003 DOID:409
Retention of urine contraindication 267064002
Neutropenic disorder contraindication 303011007 DOID:1227
Surgical procedure contraindication 387713003
Angle-closure glaucoma contraindication 392291006 DOID:13550
Myocardial infarction in recovery phase contraindication 418044006
Central nervous system depression contraindication 418072004




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.91 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
Sodium-dependent noradrenaline transporter Transporter INHIBITOR Kd 8.27 WOMBAT-PK CHEMBL
D(1A) dopamine receptor GPCR Ki 6.31 WOMBAT-PK
D(2) dopamine receptor GPCR Ki 6.18 WOMBAT-PK
Alpha-2A adrenergic receptor GPCR Ki 6.17 DRUG MATRIX
Cytochrome P450 3A4 Enzyme IC50 5.36 DRUG MATRIX
Sodium-dependent serotonin transporter Transporter Ki 5.24 PDSP
5-hydroxytryptamine receptor 2B GPCR Ki 6.67 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 7.39 DRUG MATRIX
5-hydroxytryptamine receptor 6 GPCR Ki 6.38 DRUG MATRIX
Alpha-1A adrenergic receptor GPCR IC50 9.85 WOMBAT-PK
Alpha-2B adrenergic receptor GPCR Ki 6.88 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 6.30 WOMBAT-PK
D(1B) dopamine receptor GPCR Ki 6.37 WOMBAT-PK
Histamine H1 receptor GPCR Ki 8.78 WOMBAT-PK
Histamine H2 receptor GPCR Ki 6.41 DRUG MATRIX
Muscarinic acetylcholine receptor M1 GPCR Ki 6.85 DRUG MATRIX
Muscarinic acetylcholine receptor M2 GPCR Ki 6.16 DRUG MATRIX
Muscarinic acetylcholine receptor M3 GPCR Ki 7 DRUG MATRIX
Muscarinic acetylcholine receptor M4 GPCR Ki 7.24 DRUG MATRIX
Muscarinic acetylcholine receptor M5 GPCR Ki 6.94 DRUG MATRIX
Aldehyde oxidase Enzyme IC50 5.85 WOMBAT-PK
Alpha-2C adrenergic receptor GPCR Ki 6.36 DRUG MATRIX
Sodium-dependent dopamine transporter Transporter Kd 6 WOMBAT-PK
Alpha-1D adrenergic receptor GPCR Ki 6.71 DRUG MATRIX
ATP-binding cassette sub-family G member 2 Transporter WOMBAT-PK
Voltage-dependent N-type calcium channel subunit alpha-1B Ion channel IC50 5 CHEMBL
5-hydroxytryptamine receptor 2A GPCR Ki 6.92 WOMBAT-PK
Transient receptor potential cation channel subfamily M member 3 Ion channel BLOCKER IC50 5.80 IUPHAR
Alpha-1B adrenergic receptor GPCR Ki 7.05 DRUG MATRIX
Alpha-1A adrenergic receptor GPCR IC50 6.25 CHEMBL
G protein-activated inward rectifier potassium channel 2 Ion channel BLOCKER IC50 4 IUPHAR

External reference:

IDSource
4019806 VUID
N0000147895 NUI
D00818 KEGG_DRUG
10347-81-6 SECONDARY_CAS_RN
4018785 VANDF
4019806 VANDF
C0024778 UMLSCUI
CHEBI:6690 CHEBI
CHEMBL21731 ChEMBL_ID
DB00934 DRUGBANK_ID
CHEMBL1237135 ChEMBL_ID
D008376 MESH_DESCRIPTOR_UI
4011 PUBCHEM_CID
2402 IUPHAR_LIGAND_ID
2763 INN_ID
2U1W68TROF UNII
203126 RXNORM
1567 MMSL
5023 MMSL
d00877 MMSL
001510 NDDF
004608 NDDF
10424009 SNOMEDCT_US
32823007 SNOMEDCT_US
387180003 SNOMEDCT_US
A1LX3 PDB_CHEM_ID
2U1W68TROF INXIGHT DRUGS

Pharmaceutical products:

None