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

Stem definitionDrug idCAS RN
2877 53772-83-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • zuclopenthixol
  • (Z)-Clopenthixol
  • cisordinol
  • clopixol
  • zuclopenthixol dihydrochloride
  • zuclopenthixol hydrochloride
  • zuclopenthixol HCl
Zuclopenthixol is a potent neuroleptic of the thioxanthene series with a piperazine side-chain. The antipsychotic effect of neuroleptics is related to their dopamine receptor blocking effect. The thioxanthenes have a high affinity for both the adenylate cyclase coupled dopamine D1 receptors and for the dopamine D2 receptors; in the phenothiazine group the affinity for D1 receptors is much lower than that for D2 receptors, whereas butyrophenones, diphenylbutylpiperidines and benzamides only have affinity for D2 receptors.
  • Molecular weight: 400.97
  • Formula: C22H25ClN2OS
  • CLOGP: 4.13
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 26.71
  • ALOGS: -5.19
  • ROTB: 5

Drug dosage:

DoseUnitRoute
30 mg O
15 mg P
30 mg P

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 3.56 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 49 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.678 Moderate 0.73
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.916 Moderate 0.73
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 24.099 10^-6 cm/s Moderate 0.73
dh-clint Dog hepatocyte intrinsic clearance 26.792 uL/min/10^6 cells Moderate 0.73
dppb Dog plasma protein binding (% unbound) 1.310 % Moderate 0.73
fcs-ppb Fetal calf serum protein binding (% unbound) 2.980 % Moderate 0.73
herg hERG pIC50 5.765 pIC50 Moderate 0.73
hh-clint Human hepatocyte intrinsic clearance 16.982 uL/min/10^6 cells Moderate 0.73
hlm-clint Human liver microsomal intrinsic clearance 32.359 uL/min/mg protein Moderate 0.73
hppb Human plasma protein binding (% unbound) 1.060 % Moderate 0.73
kinase-safety-class ACVR2B,AKT2,AKT3,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK2,JAK3,MAP3K7,MAPK10,MAPK12,MAPK7,MAPKAPK2,MET,MTOR,NTRK2,PDK2,PDK4,PDPK1,PIK3CB,PIM2,PRKDC,SIK2,SIK3,STK33,TEK,TTK 40
kinase-selectivity-class AXL,EPHB4,PDK4,SIK2 4
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.270 Moderate 0.73
mh-clint Mouse hepatocyte intrinsic clearance 125.026 Moderate 0.73
mppb Mouse plasma protein binding (% unbound) 1.650 Moderate 0.73
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 7.907 Moderate 0.73
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 3.750 % Moderate 0.73
rh-clint Rat hepatocyte intrinsic clearance 208.449 uL/min/10^6 cells Moderate 0.73
rh-fuinc Rat hepatocyte fraction unbound in incubation 8.430 % Moderate 0.73
rppb Rat plasma protein binding (% unbound) 1.320 % Moderate 0.73
solubility-dd Solubility at pH 7.4 in DMSO 18.967 uM Moderate 0.73

Approvals:

DateAgencyCompanyOrphan
None UK Medicines and Healthcare Products Regulatory Agency (MHRA)

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 959.69 50.91 169 5820 3097 90619361
Anosognosia 953.58 50.91 170 5819 3352 90619106
Sexual dysfunction 926.18 50.91 174 5815 4630 90617828
Disturbance in social behaviour 917.73 50.91 169 5820 4019 90618439
Metabolic disorder 873.17 50.91 178 5811 7292 90615166
Personality change 776.66 50.91 161 5828 7160 90615298
Dystonia 623.40 50.91 157 5832 16662 90605796
Sedation 580.72 50.91 187 5802 47984 90574474
Dyskinesia 575.21 50.91 174 5815 36360 90586098
Suicide attempt 498.68 50.91 187 5802 75212 90547246
Blood glucose increased 402.23 50.91 171 5818 95075 90527383
Insurance issue 162.67 50.91 50 5939 10908 90611550
Intentional self-injury 162.07 50.91 64 5925 29270 90593188
Schizophrenia 143.59 50.91 49 5940 14865 90607593
Refusal of examination 138.74 50.91 22 5967 202 90622256
Eosinophil count decreased 133.84 50.91 33 5956 3179 90619279
Drug ineffective 131.23 50.91 283 5706 1384015 89238443
Personality change due to a general medical condition 126.04 50.91 21 5968 269 90622189
Psychotic symptom 113.59 50.91 27 5962 2229 90620229
Extrapyramidal disorder 109.41 50.91 41 5948 16262 90606196
Mental impairment 101.21 50.91 39 5950 16681 90605777
Condition aggravated 95.19 50.91 153 5836 595392 90027066
Electrocardiogram QT prolonged 84.27 50.91 55 5934 72401 90550057
Neutropenia 82.04 50.91 87 5902 224817 90397641
Leukopenia 78.83 50.91 60 5929 100650 90521808
Adverse drug reaction 75.19 50.91 62 5927 116639 90505819
Intentional overdose 67.10 50.91 53 5936 93781 90528677
Treatment noncompliance 59.47 50.91 39 5950 51688 90570770
Delusion 55.38 50.91 24 5965 13816 90608642
Pain 53.91 50.91 3 5986 996338 89626120
Suicidal ideation 53.40 50.91 42 5947 73813 90548645
Hallucination, auditory 52.07 50.91 24 5965 15951 90606507

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
Dystonia 226.70 36.75 83 6750 12707 42601795
Psychotic disorder 220.75 36.75 103 6730 29105 42585397
Delusion of grandeur 213.23 36.75 52 6781 1944 42612558
Schizophrenia 200.14 36.75 72 6761 10478 42604024
Blood prolactin abnormal 195.45 36.75 43 6790 1012 42613490
Anosognosia 190.35 36.75 42 6791 1002 42613500
Hallucination, auditory 186.46 36.75 75 6758 14789 42599713
Rhinalgia 176.56 36.75 44 6789 1800 42612702
Extrapyramidal disorder 169.25 36.75 72 6761 16340 42598162
Lymphocyte count abnormal 169.11 36.75 44 6789 2143 42612359
Disturbance in social behaviour 167.53 36.75 42 6791 1761 42612741
Affective disorder 160.99 36.75 53 6780 5907 42608595
Sexual dysfunction 154.33 36.75 53 6780 6722 42607780
Sedation 137.83 36.75 76 6757 30399 42584103
Myocarditis 137.47 36.75 65 6768 18873 42595629
Metabolic disorder 126.98 36.75 42 6791 4746 42609756
Delusion 123.86 36.75 56 6777 14678 42599824
Neuroleptic malignant syndrome 123.84 36.75 63 6770 21409 42593093
Personality change 112.06 36.75 40 6793 5679 42608823
SARS-CoV-2 test positive 111.61 36.75 44 6789 8216 42606286
Neutrophil count increased 108.10 36.75 56 6777 19748 42594754
Self-injurious ideation 103.98 36.75 29 6804 1839 42612663
Priapism 103.97 36.75 39 6794 6368 42608134
Dyskinesia 100.37 36.75 58 6775 25332 42589170
Lymphocyte count decreased 95.48 36.75 58 6775 27751 42586751
Salivary hypersecretion 93.25 36.75 42 6791 10901 42603601
Psychotic symptom 88.32 36.75 27 6806 2363 42612139
Leukopenia 76.67 36.75 76 6757 74670 42539832
Alopecia 73.14 36.75 50 6783 29226 42585276
Aggression 71.25 36.75 58 6775 44105 42570397
Paranoia 63.40 36.75 35 6798 13991 42600511
Suicide attempt 60.94 36.75 54 6779 46046 42568456
Hypothermia 58.69 36.75 32 6801 12483 42602019
Intentional product misuse 58.07 36.75 60 6773 61840 42552662
Spasmodic dysphonia 57.80 36.75 14 6819 507 42613995
Torticollis 57.17 36.75 17 6816 1353 42613149
Dyspepsia 55.78 36.75 49 6784 41303 42573199
Antipsychotic drug level decreased 50.64 36.75 15 6818 1178 42613324
Patient restraint 49.25 36.75 9 6824 78 42614424
Mucosal inflammation 48.37 36.75 49 6784 49325 42565177
Seizure 47.62 36.75 76 6757 120485 42494017
Incorrect dose administered 47.26 36.75 50 6783 52924 42561578
Mental impairment 45.64 36.75 27 6806 12290 42602212
Cellulitis 42.74 36.75 51 6782 61534 42552968
Overdose 42.44 36.75 67 6766 105197 42509305
Self-destructive behaviour 40.95 36.75 10 6823 375 42614127
Blepharospasm 40.30 36.75 13 6820 1355 42613147
Sinus tachycardia 39.48 36.75 30 6803 20623 42593879
Pharyngeal dystonia 38.07 36.75 7 6826 63 42614439
Dyspnoea 37.89 36.75 12 6821 442609 42171893
Blood glucose increased 36.99 36.75 52 6781 73647 42540855
Pneumonia 36.93 36.75 11 6822 422138 42192364
Blood creatine phosphokinase increased 36.82 36.75 42 6791 48296 42566206

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 994.38 37.03 192 11402 3643 110574062
Anosognosia 982.79 37.03 192 11402 3882 110573823
Disturbance in social behaviour 941.36 37.03 192 11402 4866 110572839
Sexual dysfunction 895.49 37.03 202 11392 8328 110569377
Metabolic disorder 843.08 37.03 200 11394 10310 110567395
Dystonia 743.58 37.03 218 11376 25587 110552118
Personality change 741.72 37.03 182 11412 10820 110566885
Dyskinesia 592.09 37.03 217 11377 51229 110526476
Sedation 576.31 37.03 231 11363 69452 110508253
Suicide attempt 445.97 37.03 217 11377 103177 110474528
Blood glucose increased 354.19 37.03 202 11392 132294 110445411
Schizophrenia 318.79 37.03 110 11484 21716 110555989
Extrapyramidal disorder 249.71 37.03 99 11495 28768 110548937
Hallucination, auditory 240.51 37.03 94 11500 26303 110551402
Psychotic disorder 234.68 37.03 112 11482 50825 110526880
Delusion of grandeur 223.31 37.03 51 11543 2209 110575496
Delusion 183.10 37.03 75 11519 23680 110554025
Lymphocyte count abnormal 177.94 37.03 43 11551 2383 110575322
Rhinalgia 157.36 37.03 43 11551 3886 110573819
Insurance issue 156.88 37.03 54 11540 10558 110567147
Leukopenia 155.45 37.03 127 11467 148664 110429041
Neuroleptic malignant syndrome 151.07 37.03 73 11521 33986 110543719
Affective disorder 146.22 37.03 52 11542 11189 110566516
Eosinophil count decreased 143.48 37.03 44 11550 5974 110571731
Electrocardiogram QT prolonged 137.50 37.03 104 11490 108856 110468849
Myocarditis 135.05 37.03 65 11529 29990 110547715
Salivary hypersecretion 130.82 37.03 54 11540 17367 110560338
Mental impairment 126.69 37.03 57 11537 22582 110555123
Refusal of examination 126.34 37.03 22 11572 226 110577479
Priapism 119.41 37.03 38 11556 5823 110571882
Aggression 115.80 37.03 74 11520 59136 110518569
Neutropenia 110.35 37.03 164 11430 374456 110203249
Psychotic symptom 108.24 37.03 32 11562 3835 110573870
Drug ineffective 106.37 37.03 374 11220 1520166 109057539
Personality change due to a general medical condition 101.79 37.03 19 11575 296 110577409
Neutrophil count increased 98.20 37.03 55 11539 34597 110543108
Intentional self-injury 96.90 37.03 56 11538 37373 110540332
SARS-CoV-2 test positive 95.90 37.03 43 11551 16892 110560813
Adverse drug reaction 93.51 37.03 82 11512 105477 110472228
Lymphocyte count decreased 88.92 37.03 62 11532 57181 110520524
Drug interaction 81.80 37.03 169 11425 500014 110077691
Paranoia 81.59 37.03 42 11552 22332 110555373
Self-injurious ideation 79.63 37.03 26 11568 4320 110573385
Pain 77.61 37.03 6 11588 954949 109622756
Intentional product misuse 72.19 37.03 79 11515 132825 110444880
Arthralgia 69.09 37.03 3 11591 779629 109798076
Persecutory delusion 66.56 37.03 25 11569 6266 110571439
Agitation 66.32 37.03 70 11524 112981 110464724
Hyperprolactinaemia 61.92 37.03 24 11570 6551 110571154
Dyspnoea 57.84 37.03 22 11572 1106850 109470855
Psychomotor hyperactivity 56.94 37.03 32 11562 20245 110557460
Hypothermia 56.74 37.03 35 11559 26267 110551438
Condition aggravated 56.40 37.03 187 11407 734649 109843056
Akathisia 56.33 37.03 30 11564 17083 110560622
Schizoaffective disorder 54.39 37.03 18 11576 3118 110574587
Treatment noncompliance 51.58 37.03 50 11544 72940 110504765
Patient restraint 51.46 37.03 9 11585 95 110577610
Suicidal ideation 49.54 37.03 55 11539 93882 110483823
Rash 48.73 37.03 13 11581 820951 109756754
Seizure 47.47 37.03 84 11510 221101 110356604
Mean cell haemoglobin decreased 46.38 37.03 20 11574 7154 110570551
Torticollis 46.08 37.03 16 11578 3205 110574500
Antipsychotic drug level decreased 45.33 37.03 13 11581 1399 110576306
Pneumonia 44.80 37.03 18 11576 876696 109701009
Mean cell haemoglobin concentration decreased 43.96 37.03 18 11576 5664 110572041
Tachycardia 42.24 37.03 81 11513 226564 110351141
Self-destructive behaviour 42.00 37.03 11 11583 844 110576861
Spasmodic dysphonia 41.18 37.03 10 11584 565 110577140
Blood creatine phosphokinase increased 40.63 37.03 44 11550 73033 110504672
Headache 40.59 37.03 21 11573 882356 109695349
Leukocytosis 40.16 37.03 38 11556 53790 110523915
Metabolic syndrome 38.38 37.03 14 11580 3233 110574472
Overdose 38.10 37.03 79 11515 233715 110343990
Thinking abnormal 37.44 37.03 22 11572 15118 110562587
Incorrect dose administered 37.25 37.03 50 11544 103591 110474114
Mucosal inflammation 37.06 37.03 48 11546 96093 110481612

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N05AF05 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:37955 H<small><sub>1</sub></small>-receptor antagonist
CHEBI has role CHEBI:48279 serotonergic antagonist
CHEBI has role CHEBI:48561 dopaminergic antagonist
CHEBI has role CHEBI:65190 first generation antipsychotic

Related Drugs by ATC class:

N05AF Thioxanthene derivatives 4 drugs
chlorprothixeneclopenthixolflupentixolthiothixene

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 WOMBAT-PK DRUG LABEL
D(2) dopamine receptor GPCR ANTAGONIST WOMBAT-PK DRUG LABEL
5-hydroxytryptamine receptor 2A GPCR WOMBAT-PK
5-hydroxytryptamine receptor 6 GPCR Ki 6.77 CHEMBL
Alpha-1A adrenergic receptor GPCR WOMBAT-PK
Histone deacetylase 6 Enzyme IC50 5.47 CHEMBL

External reference:

IDSource
D03556 KEGG_DRUG
C0376160 UMLSCUI
CHEBI:51364 CHEBI
CHEMBL53904 ChEMBL_ID
D003006 MESH_DESCRIPTOR_UI
DB01624 DRUGBANK_ID
5311507 PUBCHEM_CID
7559 IUPHAR_LIGAND_ID
5443 INN_ID
58045-23-1 SECONDARY_CAS_RN
47ISU063SG UNII
102546 RXNORM
004069 NDDF
004072 NDDF
387566002 SNOMEDCT_US
426594007 SNOMEDCT_US
427940003 SNOMEDCT_US
428715002 SNOMEDCT_US
429346008 SNOMEDCT_US
C0009026 UMLSCUI
DB13841 DRUGBANK_ID
12454 PUBCHEM_CID
1315 INN_ID
47ISU063SG INXIGHT DRUGS

Pharmaceutical products:

None