cyclizine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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 µM/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
BA (Bioavailability) 47 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.725 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.370 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 26.303 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 35.645 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 15.760 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 28.570 % High 1
herg hERG pIC50 5.399 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 4.416 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 8.810 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 17.710 % High 1
kinase-safety-class ACVR2B,AKT2,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,GRK2,ITK,JAK2,MAP3K7,MAPK10,MAPK12,MAPK7,MAPKAPK2,MET,NTRK2,PDK2,PDK4,PDPK1,PIM2,PRKDC,SIK2,SIK3,TEK,TGFBR1 32
kinase-selectivity-class AXL,CDK4,ERBB2,PDK4,SIK2 5
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.198 High 1
mh-clint Mouse hepatocyte intrinsic clearance 64.714 High 1
mppb Mouse plasma protein binding (% unbound) 15.610 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.501 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 High 1
pppb Pig plasma protein binding (% unbound) 32.070 % High 1
rh-clint Rat hepatocyte intrinsic clearance 130.317 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 44.670 % High 1
rppb Rat plasma protein binding (% unbound) 19.750 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 841.395 uM High 1

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 245.26 27.40 89 10610 18041 90599707
Mucosal inflammation 173.30 27.40 99 10600 57526 90560222
Vomiting 151.04 27.40 304 10395 787989 89829759
Desmoplastic small round cell tumour 136.19 27.40 21 10678 79 90617669
Skin candida 114.78 27.40 29 10670 1712 90616036
Diarrhoea 113.22 27.40 302 10397 938888 89678860
Constipation 110.40 27.40 150 10549 280245 90337503
Pituitary tumour benign 108.95 27.40 29 10670 2103 90615645
Ejection fraction decreased 95.04 27.40 51 10648 26202 90591546
Neuropathy peripheral 84.40 27.40 92 10607 136878 90480870
Metastases to peritoneum 73.80 27.40 25 10674 4130 90613618
Hypomagnesaemia 73.21 27.40 48 10651 35540 90582208
Hypokalaemia 68.73 27.40 81 10618 131035 90486713
Hyperprolactinaemia 67.24 27.40 25 10674 5408 90612340
Excessive eye blinking 66.97 27.40 18 10681 1354 90616394
Abdominal pain 64.13 27.40 143 10556 395578 90222170
Mouth ulceration 63.54 27.40 46 10653 39928 90577820
Lower respiratory tract infection 61.70 27.40 108 10591 250551 90367197
Acute kidney injury 60.21 27.40 123 10576 320264 90297484
Lacrimation increased 59.34 27.40 38 10661 27024 90590724
Ascites 58.40 27.40 47 10652 47693 90570055
Secondary adrenocortical insufficiency 53.48 27.40 17 10682 2301 90615447
Disease progression 52.94 27.40 78 10621 156537 90461211
Metastases to lymph nodes 51.75 27.40 26 10673 11663 90606085
Lethargy 50.81 27.40 49 10650 63090 90554658
Spina bifida 49.89 27.40 13 10686 867 90616881
Nail dystrophy 49.16 27.40 14 10685 1304 90616444
Anaphylactic reaction 49.07 27.40 56 10643 87468 90530280
Cerebral ventricle dilatation 47.67 27.40 13 10686 1033 90616715
Sepsis 47.53 27.40 80 10619 179734 90438014
Rectal cancer metastatic 46.81 27.40 10 10689 280 90617468
Drug ineffective 45.87 27.40 58 10641 1384240 89233508
Hiccups 45.20 27.40 16 10683 3010 90614738
Seizure 44.51 27.40 71 10628 152558 90465190
Foetal exposure during pregnancy 43.64 27.40 38 10661 42937 90574811
Metastases to liver 43.18 27.40 32 10667 28775 90588973
Nervous system disorder 41.68 27.40 28 10671 21565 90596183
Hyponatraemia 41.55 27.40 64 10635 133474 90484274
Dizziness 40.72 27.40 157 10542 589127 90028621
Nail infection 39.95 27.40 14 10685 2558 90615190
Nausea 38.67 27.40 243 10456 1110073 89507675
Axillary pain 37.46 27.40 13 10686 2308 90615440
Neutrophil count decreased 37.13 27.40 44 10655 71488 90546260
Bone pain 37.03 27.40 41 10658 61942 90555806
Pain 36.99 27.40 38 10661 996303 89621445
Anaemia 36.76 27.40 108 10591 352694 90265054
Overflow diarrhoea 35.46 27.40 7 10692 131 90617617
Perforation 35.42 27.40 12 10687 1982 90615766
Agitation neonatal 35.36 27.40 9 10690 547 90617201
Infusion related reaction 35.26 27.40 4 10695 416776 90200972
Liver function test abnormal 34.53 27.40 36 10663 50809 90566939
Candida infection 34.35 27.40 30 10669 34027 90583721
Poor peripheral circulation 33.85 27.40 14 10685 4011 90613737
Thrombocytopenia 33.24 27.40 75 10624 208650 90409098
Abdominal discomfort 32.84 27.40 8 10691 477320 90140428
Appendicitis 31.85 27.40 18 10681 10213 90607535
Catheter site haemorrhage 31.67 27.40 13 10686 3655 90614093
Pulmonary embolism 31.66 27.40 56 10643 130764 90486984
Neutropenia 31.66 27.40 77 10622 224827 90392921
Drug hypersensitivity 31.45 27.40 8 10691 463601 90154147
Productive cough 31.39 27.40 42 10657 77021 90540727
Vaginal cellulitis 31.16 27.40 6 10693 98 90617650
Swelling 30.90 27.40 6 10693 419052 90198696
Naevus haemorrhage 30.06 27.40 6 10693 119 90617629
Genital rash 29.22 27.40 8 10691 645 90617103
Pain in jaw 29.10 27.40 32 10667 47953 90569795
Malignant neoplasm progression 28.81 27.40 48 10651 106822 90510926
Palpitations 28.64 27.40 55 10644 136673 90481075
Petit mal epilepsy 27.90 27.40 13 10686 4945 90612803
Acquired cystic kidney disease 27.81 27.40 5 10694 55 90617693

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 79.57 25.22 32 2685 15914 42602704
Febrile neutropenia 63.30 25.22 68 2649 185635 42432983
Meconium abnormal 58.42 25.22 9 2708 70 42618548
Bruxism 46.23 25.22 13 2704 2156 42616462
Necrotising enterocolitis neonatal 45.54 25.22 9 2708 322 42618296
Vomiting 44.96 25.22 72 2645 289651 42328967
Angle closure glaucoma 44.49 25.22 11 2706 1111 42617507
Dystonia 41.70 25.22 19 2698 12771 42605847
Delirium 39.27 25.22 30 2687 52489 42566129
Acute hepatic failure 36.48 25.22 19 2698 17054 42601564
Tongue disorder 34.62 25.22 13 2704 5370 42613248
Laparotomy 27.82 25.22 6 2711 331 42618287
Duodenal perforation 26.79 25.22 8 2709 1638 42616980
Malaise 25.28 25.22 47 2670 212109 42406509

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 274.09 21.42 111 12782 30635 110545771
Vomiting 185.81 21.42 358 12535 910317 109666089
Desmoplastic small round cell tumour 132.98 21.42 21 12872 97 110576309
Diarrhoea 118.87 21.42 345 12548 1139160 109437246
Mucosal inflammation 108.93 21.42 90 12803 96051 110480355
Skin candida 102.12 21.42 28 12865 2300 110574106
Pituitary tumour benign 101.00 21.42 29 12864 2818 110573588
Constipation 96.01 21.42 159 12734 357627 110218779
Neuropathy peripheral 88.92 21.42 107 12786 179170 110397236
Lower respiratory tract infection 80.40 21.42 119 12774 242987 110333419
Ejection fraction decreased 77.12 21.42 52 12841 40828 110535578
Hypomagnesaemia 67.28 21.42 56 12837 60314 110516092
Metastases to peritoneum 66.76 21.42 25 12868 5585 110570821
Mouth ulceration 65.04 21.42 50 12843 48088 110528318
Hyperprolactinaemia 62.91 21.42 25 12868 6550 110569856
Abdominal pain 62.69 21.42 165 12728 512824 110063582
Liver function test abnormal 58.89 21.42 55 12838 68895 110507511
Lethargy 58.49 21.42 63 12830 93513 110482893
Lacrimation increased 55.12 21.42 38 12855 30912 110545494
Hypokalaemia 54.18 21.42 85 12808 182363 110394043
Excessive eye blinking 52.96 21.42 16 12877 1854 110574552
Nail dystrophy 50.31 21.42 14 12879 1214 110575192
Febrile neutropenia 47.20 21.42 110 12783 316657 110259749
Metastases to lymph nodes 45.90 21.42 26 12867 15006 110561400
Rectal cancer metastatic 45.64 21.42 11 12882 540 110575866
Drug ineffective 44.58 21.42 68 12825 1520472 109055934
Poor peripheral circulation 43.82 21.42 17 12876 4180 110572226
Nausea 43.03 21.42 268 12625 1235422 109340984
Secondary adrenocortical insufficiency 42.91 21.42 17 12876 4417 110571989
Bone pain 40.95 21.42 44 12849 65089 110511317
Anaphylactic reaction 40.71 21.42 58 12835 114242 110462164
Nail infection 40.57 21.42 14 12879 2474 110573932
Metastases to liver 37.71 21.42 32 12861 35354 110541052
Bruxism 37.61 21.42 16 12877 4978 110571428
Acute kidney injury 37.57 21.42 160 12733 635270 109941136
Dystonia 37.49 21.42 28 12865 25777 110550629
Perforation 36.71 21.42 12 12881 1798 110574608
Axillary pain 36.24 21.42 13 12880 2573 110573833
Seizure 34.23 21.42 78 12815 221107 110355299
Overflow diarrhoea 32.07 21.42 7 12886 220 110576186
Abnormal loss of weight 32.02 21.42 18 12875 10239 110566167
Ascites 31.44 21.42 46 12847 92762 110483644
Vaginal cellulitis 31.24 21.42 6 12887 98 110576308
Sepsis 30.85 21.42 96 12797 327250 110249156
Pain 30.59 21.42 40 12853 954915 109621491
Nervous system disorder 30.40 21.42 27 12866 31694 110544712
Disease progression 30.23 21.42 79 12814 243955 110332451
Naevus haemorrhage 30.14 21.42 6 12887 119 110576287
Hyponatraemia 29.60 21.42 73 12820 217580 110358826
Dizziness 29.09 21.42 159 12734 698034 109878372
Angle closure glaucoma 28.99 21.42 12 12881 3487 110572919
Hallucination 28.36 21.42 46 12847 101386 110475020
Acquired cystic kidney disease 27.62 21.42 5 12888 58 110576348
Pyrexia 27.59 21.42 189 12704 898076 109678330
Palpitations 26.70 21.42 58 12835 159154 110417252
Candida infection 25.99 21.42 30 12863 47979 110528427
Catheter site haemorrhage 25.94 21.42 13 12880 5867 110570539
Hiccups 25.78 21.42 17 12876 12852 110563554
Vaginal discharge 25.06 21.42 19 12874 17889 110558517
Biliary sepsis 24.83 21.42 9 12884 1834 110574572
Weight increased 24.75 21.42 9 12884 419635 110156771
Swelling face 24.63 21.42 41 12852 92280 110484126
Dyspnoea 24.09 21.42 215 12678 1106657 109469749
Muscle twitching 23.87 21.42 23 12870 29912 110546494
Autoimmune haemolytic anaemia 23.73 21.42 15 12878 10552 110565854
Genital rash 23.68 21.42 8 12885 1327 110575079
General physical health deterioration 23.63 21.42 10 12883 425285 110151121
Swelling 23.45 21.42 6 12887 351035 110225371
Malignant neoplasm progression 23.15 21.42 58 12835 174509 110401897
Pancreatitis chronic 23.08 21.42 11 12882 4454 110571952
Lip swelling 23.07 21.42 29 12864 50638 110525768
Petit mal epilepsy 22.89 21.42 13 12880 7534 110568872
Pain in jaw 22.84 21.42 29 12864 51148 110525258
Infusion related reaction 22.77 21.42 8 12885 381154 110195252
Neutrophil count decreased 22.53 21.42 46 12847 120895 110455511
Back pain 22.32 21.42 94 12799 370902 110205504
Treatment failure 22.22 21.42 3 12890 277231 110299175
Pulmonary embolism 22.16 21.42 65 12828 214409 110361997
Tubulointerstitial nephritis 21.49 21.42 29 12864 54255 110522151

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
MeSH PA D000932 Antiemetics
MeSH PA D005765 Gastrointestinal Agents
MeSH PA D006633 Histamine Antagonists
MeSH PA D006634 Histamine H1 Antagonists
MeSH PA D018377 Neurotransmitter Agents
CHEBI has role CHEBI:35488 central nervous system depressant
CHEBI has role CHEBI:36333 local anaesthetic
CHEBI has role CHEBI:37955 H<small><sub>1</sub></small>-receptor antagonist
CHEBI has role CHEBI:48873 cholinergic antagonist
CHEBI has role CHEBI:50919 antiemetic

Related Drugs by ATC class:

R06AE Piperazine derivatives 6 drugs
buclizinecetirizinechlorcyclizinelevocetirizinemeclozineoxatomide

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




🐶 Veterinary Drug Use

None

🐶 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
155017 RXNORM
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
303-25-3 SECONDARY_CAS_RN
5897-19-8 SECONDARY_CAS_RN
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
4018771 VANDF
4018772 VANDF
4019698 VANDF
QRW9FCR9P2 INXIGHT DRUGS

Pharmaceutical products:

None