Details of the Drug

General Information of Drug (ID: DMKYD5N)

• Drug Name: Zuclopenthixol
• Synonyms: Acuphase; CLOPENTHIXOL; Cisordinol; Clopenthixolum; Clopentixol; Clopixol; Zuclopenthixolum; Zuclopentixol; Alpha Clopenthixol; Zuclopenthixolum [Latin]; Zuclopentixol [Spanish]; Acuphase (TN); Alpha-Clopenthixol; Cisordinol (TN); Clopenthixol (USAN); Clopixol (TN); Zuclopenthixol (INN); Zuclopenthixol [BAN:INN]; (Z)-4-(3-(2-Chlorothioxanthen-9-ylidene)propyl)-1-piperazineethanol; 2-[4-[(3Z)-3-(2-chlorothioxanthen-9-ylidene)propyl]piperazin-1-yl]ethanol; 2-{4-[(3Z)-3-(2-chloro-10H-dibenzo[b,e]thiopyran-10-ylidene)propyl]piperazin-1-yl}ethanol; 2-{4-[3-(2-chloro-10H-dibenzo[b,e]thiopyran-10-ylidene)propyl]piperazin-1-yl}ethanol; 4-(3-(2-Chlorothioxanthen-9-ylidene)propyl)-1-piperazineethanol

Indication

Disease Entry	ICD 11	Status	REF
Schizophrenia	6A20	Approved	[1]

• Therapeutic Class: Antipsychotic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 401
  Logarithm of the Partition Coefficient (xlogp); 4.3
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Clearance: The clearance of drug is approximately 0.9 L/min []
  Half-life: The concentration or amount of drug in body reduced by one-half in 20 hours [2]
  Metabolism: The drug is metabolized via sulphoxidation []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.56275 micromolar/kg/day [3]
  Vd: The volume of distribution (Vd) of drug is 20 L/kg []

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Tardive dyskinesia	Not Available	DRD2	OTBLXKEG	[4]
Tardive dyskinesia	Not Available	DRD3	OT0OFFKB	[4]
Tardive dyskinesia	Not Available	DRD4	OTAJTO7N	[4]

• Chemical Identifiers:
  Formula: C22H25ClN2OS
  IUPAC Name: 2-[4-[(3Z)-3-(2-chlorothioxanthen-9-ylidene)propyl]piperazin-1-yl]ethanol
  Canonical SMILES: C1CN(CCN1CC/C=C\\2/C3=CC=CC=C3SC4=C2C=C(C=C4)Cl)CCO
  InChI: InChI=1S/C22H25ClN2OS/c23-17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)27-22)5-3-9-24-10-12-25(13-11-24)14-15-26/h1-2,4-8,16,26H,3,9-15H2/b18-5-
  InChIKey: WFPIAZLQTJBIFN-DVZOWYKESA-N
• Cross-matching ID:
  PubChem CID: 5311507
  ChEBI ID: CHEBI:51364
  CAS Number: 53772-83-1
  DrugBank ID: DB01624
  TTD ID: D0I8LU
  INTEDE ID: DR1741

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Drug Response	[4]
D(3) dopamine receptor (DRD3)	OT0OFFKB	DRD3_HUMAN	Drug Response	[4]
D(4) dopamine receptor (DRD4)	OTAJTO7N	DRD4_HUMAN	Drug Response	[4]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Schizophrenia
• ICD Disease Classification: 6A20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine D2 receptor (D2R)	DTT	DRD2	2.50E-02	-0.08	-0.49
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	7.30E-01	-1.91E-02	-1.41E-01

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7559).
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [4] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [5] An ethopharmacological assessment of the effects of zuclopenthixol on agonistic interactions in male mice. Methods Find Exp Clin Pharmacol. 1999 Jan-Feb;21(1):11-5.
• [6] Genotype and co-medication dependent CYP2D6 metabolic activity: effects on serum concentrations of aripiprazole, haloperidol, risperidone, paliperidone and zuclopenthixol. Eur J Clin Pharmacol. 2016 Feb;72(2):175-84.
• [7] Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.