cyclizine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
diphenylmethyl piperazine derivatives 749 82-92-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • cyclizine
  • marezine
  • nautazine
  • cyclizine hydrochloride
  • cyclizine lactate
  • cyclizine HCl
A histamine H1 antagonist given by mouth or parenterally for the control of postoperative and drug-induced vomiting and in motion sickness. (From Martindale, The Extra Pharmacopoeia, 30th ed, p935)
  • Molecular weight: 266.39
  • Formula: C18H22N2
  • CLOGP: 3.80
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 0
  • TPSA: 6.48
  • ALOGS: -3.55
  • ROTB: 3

  • Status: OFM

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O
0.10 g P
0.30 g R

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 8.70 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 8.02 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 16.50 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 14.50 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 13.53 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
None FDA GLAXOSMITHKLINE

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
Neutropenic sepsis 230.95 21.45 89 9111 14560 53325306
Vomiting 139.22 21.45 280 8920 496859 52843007
Pituitary tumour benign 105.56 21.45 30 9170 1891 53337975
Mucosal inflammation 99.63 21.45 72 9128 42712 53297154
Lower respiratory tract infection 90.31 21.45 94 9106 90887 53248979
Hyperprolactinaemia 89.43 21.45 30 9170 3285 53336581
Desmoplastic small round cell tumour 68.30 21.45 14 9186 214 53339652
Abdominal pain 63.95 21.45 138 9062 255765 53084101
Skull malformation 56.66 21.45 13 9187 344 53339522
Secondary adrenocortical insufficiency 52.94 21.45 16 9184 1250 53338616
Diarrhoea 52.83 21.45 230 8970 625316 52714550
Constipation 49.50 21.45 107 9093 198305 53141561
Spina bifida 46.57 21.45 13 9187 767 53339099
Metastases to peritoneum 46.22 21.45 18 9182 3017 53336849
Sepsis 46.08 21.45 87 9113 146342 53193524
Neutropenia 44.53 21.45 90 9110 159095 53180771
Rectal cancer metastatic 43.79 21.45 10 9190 259 53339607
Liver function test abnormal 42.92 21.45 47 9153 48024 53291842
Cerebral ventricle dilatation 42.91 21.45 13 9187 1024 53338842
Perforation 38.75 21.45 12 9188 1017 53338849
Agitation neonatal 37.14 21.45 10 9190 515 53339351
Drug ineffective 36.53 21.45 53 9147 817192 52522674
Ejection fraction decreased 34.31 21.45 28 9172 19820 53320046
Ascites 34.00 21.45 38 9162 39697 53300169
Adrenal insufficiency 32.32 21.45 24 9176 14805 53325061
Vaginal discharge 32.31 21.45 17 9183 5736 53334130
Thrombocytopenia 31.38 21.45 72 9128 138655 53201211
Metastases to lymph nodes 30.84 21.45 18 9182 7422 53332444
Skin candida 30.14 21.45 10 9190 1057 53338809
Confusional state 28.74 21.45 86 9114 194135 53145731
Lacrimation increased 28.33 21.45 24 9176 17879 53321987
Acute kidney injury 28.24 21.45 102 9098 253766 53086100
Poor feeding infant 28.22 21.45 7 9193 260 53339606
Asthenia 28.21 21.45 12 9188 343578 52996288
Genital rash 28.13 21.45 8 9192 505 53339361
Developmental hip dysplasia 27.99 21.45 10 9190 1320 53338546
Petit mal epilepsy 27.35 21.45 13 9187 3535 53336331
Hypomagnesaemia 27.05 21.45 27 9173 24784 53315082
Anaphylactic reaction 26.72 21.45 41 9159 58285 53281581
Lethargy 26.35 21.45 39 9161 53721 53286145
Acquired cystic kidney disease 26.08 21.45 5 9195 53 53339813
Drug hypersensitivity 25.68 21.45 7 9193 265235 53074631
Inappropriate antidiuretic hormone secretion 25.64 21.45 21 9179 14930 53324936
Hyponatraemia 25.25 21.45 57 9143 108550 53231316
Oral herpes 24.86 21.45 24 9176 21155 53318711
Pain 24.44 21.45 40 9160 588358 52751508
Pyrexia 24.34 21.45 135 9065 403058 52936808
Hypokalaemia 23.95 21.45 52 9148 96465 53243401
Neuropathy peripheral 23.81 21.45 54 9146 103133 53236733
Mouth ulceration 23.31 21.45 27 9173 29299 53310567
Mania 23.25 21.45 18 9182 11811 53328055
Colitis 23.09 21.45 32 9168 41520 53298346
Naevus haemorrhage 23.08 21.45 5 9195 101 53339765
Palpitations 23.00 21.45 53 9147 102295 53237571
Foetal exposure during pregnancy 22.77 21.45 29 9171 34686 53305180
Metastases to liver 22.71 21.45 23 9177 21473 53318393
Tubulointerstitial nephritis 21.86 21.45 20 9180 16484 53323382
Nausea 21.80 21.45 212 8988 755879 52583987
Hiccups 21.76 21.45 9 9191 1761 53338105
Periorbital cellulitis 21.72 21.45 7 9193 675 53339191

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
Neutropenic sepsis 104.85 21.98 40 2795 12659 32498032
Vomiting 58.46 21.98 86 2749 235471 32275220
Bruxism 45.59 21.98 13 2822 1654 32509037
Dextrocardia 44.20 21.98 8 2827 127 32510564
Febrile neutropenia 43.93 21.98 53 2782 119513 32391178
Foetal alcohol syndrome 43.04 21.98 8 2827 148 32510543
Dystonia 36.38 21.98 18 2817 10605 32500086
Tongue disorder 32.32 21.98 13 2822 4711 32505980
Duodenal perforation 26.03 21.98 8 2827 1317 32509374
Malaise 23.22 21.98 49 2786 177089 32333602

Pharmacologic Action:

SourceCodeDescription
ATC R06AE03 RESPIRATORY SYSTEM
ANTIHISTAMINES FOR SYSTEMIC USE
ANTIHISTAMINES FOR SYSTEMIC USE
Piperazine derivatives
ATC R06AE53 RESPIRATORY SYSTEM
ANTIHISTAMINES FOR SYSTEMIC USE
ANTIHISTAMINES FOR SYSTEMIC USE
Piperazine derivatives
CHEBI has role CHEBI:35488 CNS depressants
CHEBI has role CHEBI:36333 local anaesthetics
CHEBI has role CHEBI:37955 H1-receptor blockers
CHEBI has role CHEBI:48873 Anticholinergika
CHEBI has role CHEBI:50919 antiemetico
MeSH PA D000932 Antiemetics
MeSH PA D002491 Central Nervous System Agents
MeSH PA D005765 Gastrointestinal Agents
MeSH PA D018494 Histamine Agents
MeSH PA D006633 Histamine Antagonists
MeSH PA D006634 Histamine H1 Antagonists
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018373 Peripheral Nervous System Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Vasomotor rhinitis indication 8229003 DOID:4730
Motion sickness indication 37031009 DOID:2951
Cough indication 49727002
Allergic rhinitis indication 61582004
Nasal discharge indication 64531003
Nasal congestion indication 68235000
Sneezing indication 76067001
Common cold indication 82272006 DOID:10459
Seasonal allergic rhinitis indication 367498001
Allergic conjunctivitis indication 473460002 DOID:11204
Ocular hypertension contraindication 4210003 DOID:9282
Dependent drug abuse contraindication 6525002
Peptic ulcer contraindication 13200003 DOID:750
Chronic disease of respiratory system contraindication 17097001
Mood swings contraindication 18963009
Myocardial infarction contraindication 22298006 DOID:5844
Inflammatory bowel disease contraindication 24526004 DOID:0050589
Ventricular tachycardia contraindication 25569003
Hyperthyroidism contraindication 34486009 DOID:7998
Acute hepatitis contraindication 37871000
Hypertensive disorder contraindication 38341003 DOID:10763
Disorder of gallbladder contraindication 39621005 DOID:0060262
Hypothyroidism contraindication 40930008 DOID:1459
Conduction disorder of the heart contraindication 44808001
Low blood pressure contraindication 45007003
Chronic heart failure contraindication 48447003
Bradycardia contraindication 48867003
Acidosis contraindication 51387008
Coronary arteriosclerosis contraindication 53741008 DOID:3393
Arterial thrombosis contraindication 65198009
Drug AND/OR toxin-induced diarrhea contraindication 65979008
Substance abuse contraindication 66214007
Benign intracranial hypertension contraindication 68267002 DOID:11459
Arteriosclerotic vascular disease contraindication 72092001
Diabetes mellitus contraindication 73211009 DOID:9351
Urethral stricture contraindication 76618002
Decreased respiratory function contraindication 80954004
Injury of head contraindication 82271004
Chronic idiopathic constipation contraindication 82934008
Epilepsy contraindication 84757009 DOID:1826
Kidney disease contraindication 90708001 DOID:557
Acute abdominal pain contraindication 116290004
Procedure on urinary system contraindication 118677009
Partial atrioventricular block contraindication 195039008
Acute pancreatitis contraindication 197456007 DOID:2913
Disease of liver contraindication 235856003 DOID:409
Bladder outflow obstruction contraindication 236645006
Telangiectasia disorder contraindication 247479008
Benign prostatic hyperplasia contraindication 266569009
Retention of urine contraindication 267064002
Lesion of brain contraindication 301766008
Primary adrenocortical insufficiency contraindication 373662000
Adrenal cortical hypofunction contraindication 386584007 DOID:10493
Operation on gastrointestinal tract contraindication 386621005
Hypoxia contraindication 389086002
Angle-closure glaucoma contraindication 392291006 DOID:13550
Pseudomembranous enterocolitis contraindication 397683000
Atrophoderma contraindication 399979006
Peripheral vascular disease contraindication 400047006
Disorder of coronary artery contraindication 414024009
Central nervous system depression contraindication 418072004
Ultrarapid metabolizer due to cytochrome p450 CYP2D6 variant contraindication 422681000
Dysfunction of sphincter of Oddi contraindication 430887001
Hypertensive urgency contraindication 443482000
Acute exacerbation of asthma contraindication 708038006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.19 Basic
pKa2 3.88 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
Histamine H1 receptor GPCR ANTAGONIST Ki 8.35 DRUG MATRIX CHEMBL
5-hydroxytryptamine receptor 2A GPCR Ki 7.19 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 6.62 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 6.27 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 5.99 DRUG MATRIX
Muscarinic acetylcholine receptor M1 GPCR Ki 6.79 DRUG MATRIX
Muscarinic acetylcholine receptor M2 GPCR Ki 6.39 DRUG MATRIX
Muscarinic acetylcholine receptor M3 GPCR Ki 6.80 DRUG MATRIX
Muscarinic acetylcholine receptor M4 GPCR Ki 6.92 DRUG MATRIX
Muscarinic acetylcholine receptor M5 GPCR Ki 6.34 DRUG MATRIX
Sodium-dependent dopamine transporter Transporter Ki 6.22 DRUG MATRIX
Cytochrome P450 2D6 Enzyme IC50 5.21 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 6.22 DRUG MATRIX
Amine oxidase [flavin-containing] B Enzyme WOMBAT-PK
Alpha-2A adrenergic receptor GPCR Ki 6.24 DRUG MATRIX
Alpha-1B adrenergic receptor GPCR Ki 5.86 DRUG MATRIX

External reference:

IDSource
4019698 VUID
N0000147790 NUI
D02090 KEGG_DRUG
303-25-3 SECONDARY_CAS_RN
C0010547 UMLSCUI
CHEBI:3994 CHEBI
CHEMBL648 ChEMBL_ID
CHEMBL1200497 ChEMBL_ID
DB01176 DRUGBANK_ID
CHEMBL1324714 ChEMBL_ID
D003501 MESH_DESCRIPTOR_UI
6726 PUBCHEM_CID
7151 IUPHAR_LIGAND_ID
176 INN_ID
QRW9FCR9P2 UNII
155017 RXNORM
10014 MMSL
4516 MMSL
d00858 MMSL
003395 NDDF
003396 NDDF
003397 NDDF
10133003 SNOMEDCT_US
387491004 SNOMEDCT_US
396008000 SNOMEDCT_US
85354008 SNOMEDCT_US
4018771 VANDF
4018772 VANDF
4019698 VANDF

Pharmaceutical products:

None