cyclizine ๐Ÿถ Veterinary Use | 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 ยตM/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 197.10 25.83 77 8028 14070 50582949
Mucosal inflammation 136.11 25.83 83 8022 40059 50556960
Vomiting 117.37 25.83 239 7866 460519 50136500
Pituitary tumour benign 100.76 25.83 28 8077 1753 50595266
Desmoplastic small round cell tumour 96.09 25.83 15 8090 42 50596977
Skin candida 89.71 25.83 24 8081 1302 50595717
Lower respiratory tract infection 83.60 25.83 89 8016 95112 50501907
Hyperprolactinaemia 71.50 25.83 25 8080 3340 50593679
Constipation 70.71 25.83 115 7990 185593 50411426
Diarrhoea 68.79 25.83 228 7877 588248 50008771
Secondary adrenocortical insufficiency 55.73 25.83 16 8089 1127 50595892
Abdominal pain 54.45 25.83 118 7987 236110 50360909
Ejection fraction decreased 51.95 25.83 34 8071 18486 50578533
Spina bifida 48.97 25.83 13 8092 684 50596335
Metastases to peritoneum 48.72 25.83 18 8087 2815 50594204
Hypomagnesaemia 47.33 25.83 35 8070 23121 50573898
Lacrimation increased 47.19 25.83 31 8074 16961 50580058
Drug ineffective 46.67 25.83 38 8067 819295 49777724
Mouth ulceration 45.60 25.83 37 8068 27987 50569032
Rectal cancer metastatic 45.25 25.83 10 8095 240 50596779
Cerebral ventricle dilatation 45.16 25.83 13 8092 924 50596095
Hypokalaemia 41.14 25.83 60 8045 87932 50509087
Perforation 40.40 25.83 12 8093 952 50596067
Nail dystrophy 37.97 25.83 11 8094 800 50596219
Sepsis 37.18 25.83 72 8033 132853 50464166
Ascites 35.88 25.83 36 8069 35825 50561194
Neuropathy peripheral 35.49 25.83 59 8046 96698 50500321
Agitation neonatal 33.53 25.83 9 8096 494 50596525
Anaphylactic reaction 33.05 25.83 42 8063 54013 50543006
Metastases to lymph nodes 33.05 25.83 18 8087 7006 50590013
Excessive eye blinking 32.05 25.83 10 8095 936 50596083
Neutrophil count decreased 31.75 25.83 38 8067 45988 50551031
Acute kidney injury 31.59 25.83 94 8011 227964 50369055
Lethargy 31.16 25.83 39 8066 49393 50547626
Hiccups 29.72 25.83 11 8094 1728 50595291
Genital rash 29.67 25.83 8 8097 447 50596572
Neutropenia 29.65 25.83 70 8035 147895 50449124
Poor feeding infant 29.36 25.83 7 8098 237 50596782
Petit mal epilepsy 29.21 25.83 13 8092 3276 50593743
Pain 29.11 25.83 30 8075 578873 50018146
Vaginal discharge 29.10 25.83 15 8090 5225 50591794
Nail infection 28.33 25.83 11 8094 1970 50595049
Nervous system disorder 27.62 25.83 22 8083 16201 50580818
Thrombocytopenia 27.33 25.83 62 8043 127611 50469408
Axillary pain 27.00 25.83 10 8095 1574 50595445
Acquired cystic kidney disease 26.81 25.83 5 8100 49 50596970
Dizziness 26.78 25.83 118 7987 346251 50250768

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 69.56 28.28 27 1947 11700 29560853
Meconium abnormal 52.18 28.28 8 1966 57 29572496
Febrile neutropenia 50.96 28.28 49 1925 112191 29460362
Bruxism 49.68 28.28 13 1961 1574 29570979
Dystonia 45.85 28.28 19 1955 9730 29562823
Necrotising enterocolitis neonatal 42.77 28.28 8 1966 203 29572350
Tongue disorder 35.94 28.28 13 1961 4623 29567930
Vomiting 34.20 28.28 55 1919 212205 29360348
Duodenal perforation 29.05 28.28 8 1966 1174 29571379
Toxic encephalopathy 28.67 28.28 11 1963 4601 29567952

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
Neutropenic sepsis 213.10 21.65 92 9560 23180 64465900
Vomiting 144.30 21.65 278 9374 550839 63938241
Lower respiratory tract infection 98.43 21.65 94 9558 94520 64394560
Pituitary tumour benign 95.63 21.65 28 9624 2265 64486815
Desmoplastic small round cell tumour 93.60 21.65 15 9637 57 64489023
Mucosal inflammation 88.54 21.65 74 9578 62510 64426570
Skin candida 80.84 21.65 23 9629 1680 64487400
Diarrhoea 77.43 21.65 260 9392 722444 63766636
Hyperprolactinaemia 68.54 21.65 25 9627 4040 64485040
Constipation 66.18 21.65 121 9531 229216 64259864
Abdominal pain 55.33 21.65 135 9517 312240 64176840
Mouth ulceration 49.27 21.65 40 9612 32404 64456676
Lacrimation increased 46.93 21.65 31 9621 18315 64470765
Metastases to peritoneum 45.97 21.65 18 9634 3529 64485551
Secondary adrenocortical insufficiency 45.48 21.65 16 9636 2329 64486751
Neuropathy peripheral 40.33 21.65 67 9585 117458 64371622
Rectal cancer metastatic 40.10 21.65 10 9642 439 64488641
Perforation 39.14 21.65 12 9640 1136 64487944
Nail dystrophy 38.68 21.65 11 9641 802 64488278
Ejection fraction decreased 38.62 21.65 33 9619 28674 64460406
Dystonia 36.82 21.65 27 9625 18838 64470242
Hypomagnesaemia 36.67 21.65 36 9616 37340 64451740
Liver function test abnormal 35.33 21.65 44 9608 59357 64429723
Febrile neutropenia 35.19 21.65 83 9569 187574 64301506
Vaginal discharge 33.94 21.65 15 9637 3982 64485098
Drug ineffective 32.81 21.65 47 9605 840200 63648880
Lethargy 32.77 21.65 47 9605 72547 64416533
Metastases to lymph nodes 30.56 21.65 18 9634 8699 64480381
Abnormal loss of weight 30.55 21.65 17 9635 7383 64481697
Nail infection 29.80 21.65 11 9641 1836 64487244
Hypokalaemia 29.77 21.65 60 9592 121843 64367237
Pyrexia 29.77 21.65 163 9489 558481 63930599
Anaphylactic reaction 28.88 21.65 43 9609 68621 64420459
Bruxism 28.85 21.65 13 9639 3611 64485469
Poor peripheral circulation 27.14 21.65 12 9640 3188 64485892
Axillary pain 26.79 21.65 10 9642 1722 64487358
Acquired cystic kidney disease 26.46 21.65 5 9647 57 64489023
Bone pain 26.32 21.65 34 9618 47538 64441542
Genital rash 25.09 21.65 8 9644 861 64488219
Petit mal epilepsy 24.79 21.65 13 9639 5019 64484061
Sepsis 24.53 21.65 83 9569 230258 64258822
Naevus haemorrhage 23.69 21.65 5 9647 103 64488977
Drug hypersensitivity 22.90 21.65 4 9648 237811 64251269
Pancreatitis chronic 22.77 21.65 11 9641 3575 64485505
Adrenal insufficiency 22.69 21.65 22 9630 22465 64466615
Palpitations 22.66 21.65 49 9603 104439 64384641
Excessive eye blinking 22.17 21.65 8 9644 1252 64487828
Ascites 22.13 21.65 36 9616 61965 64427115
Muscle twitching 21.88 21.65 20 9632 18978 64470102
Tubulointerstitial nephritis 21.83 21.65 25 9627 30884 64458196

FDA Adverse Event Reporting System (Pediatric)

None

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 central nervous system depressants
CHEBI has role CHEBI:36333 local anesthetics
CHEBI has role CHEBI:37955 H1 receptor antagonists
CHEBI has role CHEBI:48873 acetylcholine receptor antagonist
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 | Suggest Off label Use Form| |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




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 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
5897-19-8 SECONDARY_CAS_RN
155017 RXNORM
4018771 VANDF
4018772 VANDF
4019698 VANDF
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
10014 MMSL
4516 MMSL
d00858 MMSL
003395 NDDF
003396 NDDF
003397 NDDF
10133003 SNOMEDCT_US
387491004 SNOMEDCT_US
396008000 SNOMEDCT_US
85354008 SNOMEDCT_US

Pharmaceutical products:

None