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

Stem definition	Drug id	CAS RN
diphenylmethyl piperazine derivatives	749	82-92-8

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
0.10	g	O
0.10	g	P
0.30	g	R

ADMET properties:

Property	Value	Reference
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

Approvals:

Date	Agency	Company	Orphan
None	FDA	GLAXOSMITHKLINE

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Histamine H1 receptor	GPCR	P35367	HRH1_HUMAN	ANTAGONIST	Ki	8.35	DRUG MATRIX	CHEMBL
5-hydroxytryptamine receptor 2A	GPCR	P28223	5HT2A_HUMAN		Ki	7.19	DRUG MATRIX
5-hydroxytryptamine receptor 2B	GPCR	P41595	5HT2B_HUMAN		Ki	6.62	DRUG MATRIX
5-hydroxytryptamine receptor 2C	GPCR	P28335	5HT2C_HUMAN		Ki	6.27	DRUG MATRIX
D(3) dopamine receptor	GPCR	P35462	DRD3_HUMAN		Ki	5.99	DRUG MATRIX
Muscarinic acetylcholine receptor M1	GPCR	P11229	ACM1_HUMAN		Ki	6.79	DRUG MATRIX
Muscarinic acetylcholine receptor M2	GPCR	P08172	ACM2_HUMAN		Ki	6.39	DRUG MATRIX
Muscarinic acetylcholine receptor M3	GPCR	P20309	ACM3_HUMAN		Ki	6.80	DRUG MATRIX
Muscarinic acetylcholine receptor M4	GPCR	P08173	ACM4_HUMAN		Ki	6.92	DRUG MATRIX
Muscarinic acetylcholine receptor M5	GPCR	P08912	ACM5_HUMAN		Ki	6.34	DRUG MATRIX
Sodium-dependent dopamine transporter	Transporter	Q01959	SC6A3_HUMAN		Ki	6.22	DRUG MATRIX
Cytochrome P450 2D6	Enzyme	P10635	CP2D6_HUMAN		IC50	5.21	DRUG MATRIX
Alpha-1D adrenergic receptor	GPCR	P25100	ADA1D_HUMAN		Ki	6.22	DRUG MATRIX
Amine oxidase [flavin-containing] B	Enzyme	P27338	AOFB_HUMAN				WOMBAT-PK
Alpha-2A adrenergic receptor	GPCR	P08913	ADA2A_HUMAN		Ki	6.24	DRUG MATRIX
Alpha-1B adrenergic receptor	GPCR		ADA1B_RAT		Ki	5.86	DRUG MATRIX

External reference:

ID	Source
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