Details of the Drug

General Information of Drug (ID: DM9G7BS)

• Drug Name: Cyclizine
• Synonyms: Ciclizina; Cyclizinum; Emoquil; Marezine; Nautazine; Valoid; Wellcome; Cyclizine chloride; Cyclizine hydrochloride; Marezine hydrochloride; BW 47-83; Ciclizina [INN-Spanish]; Cyclizine (INN); Cyclizinum [INN-Latin]; Emoquil (TN); Marezine (TN); Marzine (TN); Ne-devomit; Neo-devomit; Reis-fit; Valoid (TN); Wellcome preparation 47-83; Wellcome prepn 47-83; Cyclizine [INN:BAN:DCF]; Wellcome prepn. 47-83; N-Benzhydryl-N'-methylpiperazine; N-Methyl-N'-benzhydrylpiperazine; N-Methyl-N'-benzyhydrylpiperazine; (+-)-1-diphenylmethyl-4-methylpiperazine; (-)-1-Diphenylmethyl-4-methylpiperazine; (N-Benzhydryl)(N'-methyl)diethylenediamine; 1-(Diphenylmethyl)-4-methylpiperazine; 1-Benzhydryl-4-methylpiperazin; 1-Benzhydryl-4-methylpiperazine; 1-Diphenylmethyl-4-methylpiperazine

Indication

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[1]
Common cold	CA00	Approved	[1]
Cough	MD12	Approved	[1]
Nausea	MD90	Approved	[2]
Seasonal allergic rhinitis	CA08.01	Approved	[1]
Vasomotor/allergic rhinitis	CA08	Approved	[1]

• Therapeutic Class: Antiemetics
• Affected Organisms: Humans and other mammals
• ATC Code:
  R06AE03: Cyclizine
  R06AE: Piperazine derivatives
  R06A: ANTIHISTAMINES FOR SYSTEMIC USE
  R06: ANTIHISTAMINES FOR SYSTEMIC USE
  R: RESPIRATORY SYSTEM
  R06AE03: Cyclizine
  R06AE: Piperazine derivatives
  R06A: ANTIHISTAMINES FOR SYSTEMIC USE
  R06: ANTIHISTAMINES FOR SYSTEMIC USE
  R: RESPIRATORY SYSTEM
  R06AE03: Cyclizine
  R06AE: Piperazine derivatives
  R06A: ANTIHISTAMINES FOR SYSTEMIC USE
  R06: ANTIHISTAMINES FOR SYSTEMIC USE
  R: RESPIRATORY SYSTEM
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 266.4
  Logarithm of the Partition Coefficient (xlogp); 3.6
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 14.5 mL/min/kg [4]
  Elimination: 0.5% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 20 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 8.0151 micromolar/kg/day [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 16.5 L/kg [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 8.7 mg/mL [3]
• Chemical Identifiers:
  Formula: C18H22N2
  IUPAC Name: 1-benzhydryl-4-methylpiperazine
  Canonical SMILES: CN1CCN(CC1)C(C2=CC=CC=C2)C3=CC=CC=C3
  InChI: InChI=1S/C18H22N2/c1-19-12-14-20(15-13-19)18(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18H,12-15H2,1H3
  InChIKey: UVKZSORBKUEBAZ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 6726
  ChEBI ID: CHEMBL648
  CAS Number: 82-92-8
  UNII: QRW9FCR9P2
  DrugBank ID: DB01176
  TTD ID: D08HRJ
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
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• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histamine H1 receptor (H1R)	TTTIBOJ	HRH1_HUMAN	Antagonist	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Allergic rhinitis
• ICD Disease Classification: CA08.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Histamine H1 receptor (H1R)	DTT	HRH1	6.74E-01	0.13	0.43

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Cyclizine

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Metoclopramide	DMFA5MY	Moderate	Antagonize the effect of Cyclizine when combined with Metoclopramide.	Nausea/vomiting [MD90]	[7]

Coadministration of a Drug Treating the Disease Different from Cyclizine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Mepyramine	DMB4SFH	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Mepyramine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[8]
Phenyltoloxamine	DMKAEQW	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Phenyltoloxamine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[8]
Cariprazine	DMJYDVK	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Cariprazine.	Bipolar disorder [6A60]	[9]
Acetylcholine	DMDF79Z	Moderate	Antagonize the effect of Cyclizine when combined with Acetylcholine.	Cataract [9B10]	[10]
Umeclidinium	DM4E8O9	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Umeclidinium.	Chronic obstructive pulmonary disease [CA22]	[11]
Tiotropium	DMFDC0Q	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Tiotropium.	Chronic obstructive pulmonary disease [CA22]	[11]
Revefenacin	DMMP5SI	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[11]
Isocarboxazid	DMAF1NB	Moderate	Additive CNS depression effects by the combination of Cyclizine and Isocarboxazid.	Depression [6A70-6A7Z]	[12]
OPC-34712	DMHG57U	Moderate	Additive anticholinergic effects by the combination of Cyclizine and OPC-34712.	Depression [6A70-6A7Z]	[9]
Clomipramine	DMINRKW	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Clomipramine.	Depression [6A70-6A7Z]	[9]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Cyclizine and Esketamine.	Depression [6A70-6A7Z]	[13]
Mepenzolate	DM8YU2F	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Mepenzolate.	Digestive system disease [DE2Z]	[8]
Solifenacin	DMG592Q	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Solifenacin.	Functional bladder disorder [GC50]	[9]
Belladonna	DM2RBWK	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[9]
ITI-007	DMUQ1DO	Moderate	Additive anticholinergic effects by the combination of Cyclizine and ITI-007.	Insomnia [7A00-7A0Z]	[9]
R0-93877	DMM4U9G	Moderate	Antagonize the effect of Cyclizine when combined with R0-93877.	Irritable bowel syndrome [DD91]	[14]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Cyclizine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[15]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Cyclizine and Lasmiditan.	Migraine [8A80]	[16]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Cyclizine and Flibanserin.	Mood disorder [6A60-6E23]	[17]
Methylscopolamine	DM5VWOB	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Methylscopolamine.	Peptic ulcer [DA61]	[9]
Quetiapine	DM1N62C	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Quetiapine.	Schizophrenia [6A20]	[9]
Aripiprazole	DM3NUMH	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Aripiprazole.	Schizophrenia [6A20]	[9]
Iloperidone	DM6AUFY	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Iloperidone.	Schizophrenia [6A20]	[9]
Paliperidone	DM7NPJS	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Paliperidone.	Schizophrenia [6A20]	[9]
Molindone	DMAH70G	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Molindone.	Schizophrenia [6A20]	[9]
Thiothixene	DMDINC4	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Thiothixene.	Schizophrenia [6A20]	[9]
Asenapine	DMSQZE2	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Asenapine.	Schizophrenia [6A20]	[9]
Acrivastine	DMTIGA0	Moderate	Additive anticholinergic effects by the combination of Cyclizine and Acrivastine.	Vasomotor/allergic rhinitis [CA08]	[8]

References

• [1] Cyclizine FDA Label
• [2] 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: 7151).
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] 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
• [6] Histamine H1-receptor antagonists, promethazine and homochlorcyclizine, increase the steady-state plasma concentrations of haloperidol and reduced haloperidol. Ther Drug Monit. 2003 Apr;25(2):192-6.
• [7] Product Information. Motilium (domperidone). Janssen-Ortho Inc, Toronto, ON.
• [8] Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82. [PMID: 7202232]
• [9] Cohen MA, Alfonso CA, Mosquera M. Development of urinary retention during treatment with clozapine and meclizine [published correction appears in Am J Psychiatry 1994 Jun;151(6):952]. Am J Psychiatry. 1994;151(4):619-620. [PMID: 8147469]
• [10] Multum Information Services, Inc. Expert Review Panel.
• [11] Cole JM, Sheehan AH, Jordan JK "Concomitant use of ipratropium and tiotropium in chronic obstructive plmonary disease." Ann Pharmacother 46 (2012): 1717-21. [PMID: 23170031]
• [12] Canadian Pharmacists Association.
• [13] Cerner Multum, Inc. "Australian Product Information.".
• [14] EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
• [15] Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
• [16] Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
• [17] Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.