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

Stem definitionDrug idCAS RN
1211 2709-56-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • flupentixol hydrochloride
  • flupenthixol
  • fluanxol
  • flupentixol
  • fluxanxol
  • flupentixol dihydrochloride
  • N-7009
  • flupentixol HCl
A thioxanthene neuroleptic that, unlike CHLORPROMAZINE, is claimed to have CNS-activating properties. It is used in the treatment of psychoses although not in excited or manic patients. (From Martindale, The Extra Pharmacopoeia, 30th ed, p595)
  • Molecular weight: 434.52
  • Formula: C23H25F3N2OS
  • CLOGP: 4.34
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 26.71
  • ALOGS: -5.04
  • ROTB: 6

Drug dosage:

DoseUnitRoute
6 mg O
4 mg P

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.10 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 40 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
CL (Clearance) 4.14 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 34.20 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.924 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.895 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 23.878 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 23.121 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 1.150 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 3.330 % High 1
herg hERG pIC50 5.833 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 12.735 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 26.424 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 1.010 % High 1
kinase-safety-class ACVR2B,AKT2,AKT3,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,GRK2,ITK,MAP3K7,MAPK10,MET,NTRK2,PDK2,PDK4,PDPK1,PIK3CB,PIM2,PRKDC,TEK 27
kinase-selectivity-class AXL,EPHB4,PDK4 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.104 High 1
mh-clint Mouse hepatocyte intrinsic clearance 65.615 High 1
mppb Mouse plasma protein binding (% unbound) 1.720 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 6.577 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 1
pppb Pig plasma protein binding (% unbound) 2.960 % High 1
rh-clint Rat hepatocyte intrinsic clearance 127.938 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 5.300 % High 1
rppb Rat plasma protein binding (% unbound) 1.250 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 15.524 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 1, 1964 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
Blood prolactin abnormal 1385.95 95.25 222 4298 3044 90620883
Anosognosia 1383.61 95.25 224 4296 3298 90620629
Disturbance in social behaviour 1330.80 95.25 222 4298 3966 90619961
Sexual dysfunction 1300.36 95.25 222 4298 4582 90619345
Metabolic disorder 1202.49 95.25 222 4298 7248 90616679
Personality change 1149.00 95.25 213 4307 7108 90616819
Dystonia 911.16 95.25 202 4318 16617 90607310
Dyskinesia 880.67 95.25 228 4292 36306 90587621
Sedation 855.16 95.25 236 4284 47935 90575992
Suicide attempt 771.73 95.25 241 4279 75158 90548769
Blood glucose increased 649.33 95.25 224 4296 95022 90528905
Drug ineffective 211.32 95.25 297 4223 1384001 89239926
Insurance issue 194.90 95.25 54 4466 10904 90613023
Adverse drug reaction 163.07 95.25 90 4430 116611 90507316
Condition aggravated 153.19 95.25 167 4353 595378 90028549
Personality change due to a general medical condition 131.96 95.25 21 4499 269 90623658

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
Antipsychotic drug level below therapeutic 574.97 82.90 116 3947 3088 42614184
Therapeutic product effect variable 554.53 82.90 112 3951 2997 42614275
Disinhibition 552.38 82.90 116 3947 3779 42613493
Obsessive-compulsive disorder 536.35 82.90 125 3938 6618 42610654
Akathisia 511.24 82.90 131 3932 10320 42606952
Euphoric mood 494.05 82.90 116 3947 6337 42610935
Increased appetite 466.81 82.90 118 3945 8788 42608484
Suicide attempt 444.50 82.90 166 3897 45934 42571338
Leukaemia 255.84 82.90 67 3996 5705 42611567
Therapeutic product effect incomplete 219.08 82.90 115 3948 70824 42546448
Anosognosia 218.28 82.90 43 4020 1001 42616271
Blood prolactin abnormal 217.83 82.90 43 4020 1012 42616260
Weight increased 216.91 82.90 132 3931 107851 42509421
Dyslipidaemia 206.19 82.90 63 4000 9355 42607917
Leukopenia 205.04 82.90 112 3951 74634 42542638
Disturbance in social behaviour 194.85 82.90 43 4020 1760 42615512
Obesity 186.63 82.90 67 3996 16392 42600880
Prescribed overdose 167.02 82.90 58 4005 12869 42604403
Dyskinesia 161.77 82.90 68 3995 25322 42591950
Metabolic disorder 153.14 82.90 43 4020 4745 42612527
Drug ineffective 149.49 82.90 235 3828 629962 41987310
Sexual dysfunction 146.86 82.90 45 4018 6730 42610542
Dystonia 133.49 82.90 49 4014 12741 42604531
Schizoaffective disorder 127.60 82.90 31 4032 1939 42615333
Personality change 124.00 82.90 38 4025 5681 42611591
Toxicity to various agents 110.95 82.90 122 3941 229014 42388258
Sedation 92.61 82.90 49 4014 30426 42586846
Irritability 87.66 82.90 46 4017 28082 42589190

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
Blood prolactin abnormal 1434.03 71.23 242 6740 3593 110578724
Anosognosia 1433.19 71.23 244 6738 3830 110578487
Disturbance in social behaviour 1367.12 71.23 242 6740 4816 110577501
Sexual dysfunction 1253.15 71.23 244 6738 8286 110574031
Metabolic disorder 1190.47 71.23 242 6740 10268 110572049
Personality change 1120.76 71.23 232 6750 10770 110571547
Dyskinesia 927.46 71.23 269 6713 51177 110531140
Suicide attempt 919.55 71.23 315 6667 103079 110479238
Dystonia 903.95 71.23 228 6754 25577 110556740
Sedation 830.37 71.23 265 6717 69418 110512899
Blood glucose increased 601.67 71.23 247 6735 132249 110450068
Drug ineffective 261.97 71.23 392 6590 1520148 109062169
Antipsychotic drug level below therapeutic 214.07 71.23 43 6939 1692 110580625
Therapeutic product effect variable 194.83 71.23 43 6939 2675 110579642
Obsessive-compulsive disorder 194.81 71.23 52 6930 7189 110575128
Insurance issue 192.74 71.23 56 6926 10556 110571761
Disinhibition 188.73 71.23 43 6939 3091 110579226
Akathisia 182.35 71.23 60 6922 17053 110565264
Adverse drug reaction 161.99 71.23 94 6888 105465 110476852
Condition aggravated 158.51 71.23 212 6770 734624 109847693
Euphoric mood 144.56 71.23 43 6939 8784 110573533
Increased appetite 141.61 71.23 48 6934 14929 110567388
Dyslipidaemia 119.53 71.23 43 6939 15922 110566395
Schizoaffective disorder 115.88 71.23 29 6953 3107 110579210
Personality change due to a general medical condition 111.43 71.23 19 6963 296 110582021
Parkinsonism 98.95 71.23 41 6941 22146 110560171
Irritability 79.73 71.23 45 6937 47764 110534553
Leukaemia 74.62 71.23 25 6957 7493 110574824

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N05AF01 NERVOUS SYSTEM
PSYCHOLEPTICS
ANTIPSYCHOTICS
Thioxanthene derivatives
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D011619 Psychotropic Drugs
MeSH PA D014150 Antipsychotic Agents
MeSH PA D015259 Dopamine Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018492 Dopamine Antagonists
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:35474 anxiolytic drug
CHEBI has role CHEBI:37890 ฮฑ-adrenergic antagonist
CHEBI has role CHEBI:48561 dopaminergic antagonist
CHEBI has role CHEBI:65190 first generation antipsychotic
CHEBI has role CHEBI:76779 EC 3.4.21.26 (prolyl oligopeptidase) inhibitor
CHEBI has role CHEBI:35476 antipsychotic agent

Related Drugs by ATC class:

N05AF Thioxanthene derivatives 4 drugs
chlorprothixeneclopenthixolthiothixenezuclopenthixol

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

DiseaseRelationSNOMED_IDDOID
Schizophrenia indication 58214004 DOID:5419




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 8.19 Basic
pKa2 4.19 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
D(1A) dopamine receptor GPCR ANTAGONIST Ki 8.40 IUPHAR IUPHAR
D(2) dopamine receptor GPCR ANTAGONIST Ki 8.82 IUPHAR IUPHAR
Sigma non-opioid intracellular receptor 1 Membrane receptor IC50 8.65 CHEMBL
5-hydroxytryptamine receptor 1A GPCR Ki 5.10 PDSP
5-hydroxytryptamine receptor 2A GPCR Ki 7.06 PDSP
Alpha-1A adrenergic receptor GPCR WOMBAT-PK
D(3) dopamine receptor GPCR ANTAGONIST Ki 8.96 IUPHAR
D(1B) dopamine receptor GPCR ANTAGONIST Ki 8.10 IUPHAR
Histamine H1 receptor GPCR Ki 9.07 PDSP
D(4) dopamine receptor GPCR Ki 8.80 PDSP
Potassium channel subfamily K member 2 Ion channel IC50 5.70 CHEMBL
Histone deacetylase 6 Enzyme IC50 5.81 CHEMBL
Solute carrier family 22 member 1 Transporter IC50 4.05 CHEMBL
D(1A) dopamine receptor GPCR Ki 7.75 CHEMBL
D(1A) dopamine receptor GPCR IC50 9.52 CHEMBL
Dopamine receptor GPCR IC50 8.52 CHEMBL

External reference:

IDSource
D01044 KEGG_DRUG
C0016367 UMLSCUI
CHEBI:5121 CHEBI
CHEMBL6066864 ChEMBL_ID
DB00875 DRUGBANK_ID
948 IUPHAR_LIGAND_ID
1745 INN_ID
2413-38-9 SECONDARY_CAS_RN
21HMQ851IS UNII
5281881 PUBCHEM_CID
235742 RXNORM
003477 NDDF
003479 NDDF
387567006 SNOMEDCT_US
442075003 SNOMEDCT_US
96220002 SNOMEDCT_US
D005475 MESH_DESCRIPTOR_UI

Pharmaceutical products:

None