Scroll

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	219.04	25.26	85	9404	16353	63463180
Mucosal inflammation	173.20	25.26	100	9389	46828	63432705
Vomiting	146.49	25.26	282	9207	559335	62920198
Desmoplastic small round cell tumour	132.10	25.26	21	9468	75	63479458
Skin candida	114.24	25.26	30	9459	1625	63477908
Pituitary tumour benign	104.09	25.26	29	9460	1966	63477567
Diarrhoea	96.13	25.26	278	9211	715088	62764445
Ejection fraction decreased	91.51	25.26	51	9438	22281	63457252
Constipation	89.65	25.26	137	9352	224806	63254727
Lower respiratory tract infection	87.13	25.26	103	9386	132204	63347329
Metastases to peritoneum	76.54	25.26	26	9463	3416	63476117
Hypomagnesaemia	69.85	25.26	47	9442	28690	63450843
Hyperprolactinaemia	69.58	25.26	25	9464	3875	63475658
Excessive eye blinking	64.00	25.26	18	9471	1262	63478271
Neuropathy peripheral	62.72	25.26	81	9408	113586	63365947
Lacrimation increased	60.59	25.26	38	9451	20593	63458940
Secondary adrenocortical insufficiency	57.65	25.26	17	9472	1411	63478122
Mouth ulceration	57.32	25.26	44	9445	32940	63446593
Abdominal pain	56.60	25.26	131	9358	293325	63186208
Metastases to lymph nodes	54.81	25.26	26	9463	8132	63471401
Hypokalaemia	52.66	25.26	71	9418	103733	63375800
Ascites	49.20	25.26	44	9445	40684	63438849
Nail dystrophy	49.13	25.26	14	9475	1029	63478504
Drug ineffective	48.67	25.26	51	9438	1044714	62434819
Spina bifida	47.17	25.26	13	9476	846	63478687
Anaphylactic reaction	46.01	25.26	53	9436	66047	63413486
Rectal cancer metastatic	45.70	25.26	10	9479	246	63479287
Cerebral ventricle dilatation	44.85	25.26	13	9476	1016	63478517
Lethargy	44.28	25.26	48	9441	55959	63423574
Disease progression	43.57	25.26	71	9418	122687	63356846
Hiccups	42.44	25.26	15	9474	2216	63477317
Metastases to liver	42.09	25.26	32	9457	23607	63455926
Pain	41.87	25.26	30	9459	740598	62738935
Nervous system disorder	41.58	25.26	29	9460	18737	63460796
Sepsis	40.69	25.26	78	9411	153045	63326488
Nail infection	40.64	25.26	15	9474	2508	63477025
Neutrophil count decreased	38.87	25.26	45	9444	56361	63423172
Perforation	38.80	25.26	12	9477	1171	63478362
Axillary pain	36.46	25.26	13	9476	1970	63477563
Seizure	35.77	25.26	68	9421	132566	63346967
Vaginal discharge	34.94	25.26	20	9469	9178	63470355
Hyponatraemia	34.76	25.26	61	9428	111839	63367694
Overflow diarrhoea	34.67	25.26	7	9482	115	63479418
Acute kidney injury	33.73	25.26	101	9388	263314	63216219
Agitation neonatal	33.56	25.26	9	9480	528	63479005
Bone pain	33.38	25.26	41	9448	54600	63424933
Candida infection	32.99	25.26	30	9459	28321	63451212
Poor peripheral circulation	31.63	25.26	14	9475	3735	63475798
Appendicitis	31.55	25.26	18	9471	8211	63471322
Catheter site haemorrhage	30.52	25.26	13	9476	3162	63476371
Joint swelling	30.47	25.26	6	9483	327660	63151873
Drug hypersensitivity	30.38	25.26	5	9484	310682	63168851
Swelling	30.38	25.26	3	9486	275375	63204158
Productive cough	30.17	25.26	42	9447	63166	63416367
Vaginal cellulitis	30.05	25.26	6	9483	93	63479440
Dizziness	29.75	25.26	135	9354	429790	63049743
Abdominal discomfort	29.58	25.26	6	9483	320879	63158654
Neutropenia	29.24	25.26	74	9415	174931	63304602
Genital rash	28.51	25.26	8	9481	556	63478977
Naevus haemorrhage	28.37	25.26	6	9483	125	63479408
Petit mal epilepsy	28.30	25.26	13	9476	3781	63475752
Anaemia	28.13	25.26	102	9387	293328	63186205
Poor feeding infant	26.94	25.26	7	9482	363	63479170
Infusion related reaction	26.24	25.26	3	9486	245518	63234015
Acquired cystic kidney disease	26.15	25.26	5	9484	61	63479472

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	84.98	27.50	32	2140	13735	34941024
Febrile neutropenia	58.59	27.50	56	2116	136793	34817966
Meconium abnormal	58.31	27.50	9	2163	73	34954686
Bruxism	49.45	27.50	13	2159	1722	34953037
Necrotising enterocolitis neonatal	48.33	27.50	9	2163	240	34954519
Dystonia	45.20	27.50	19	2153	10826	34943933
Vomiting	37.51	27.50	60	2112	247561	34707198
Tongue disorder	35.06	27.50	13	2159	5326	34949433
Duodenal perforation	29.00	27.50	8	2164	1270	34953489
Laparotomy	28.12	27.50	6	2166	323	34954436
Toxic encephalopathy	28.05	27.50	11	2161	5238	34949521

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	244.60	22.48	104	11073	26960	79706251
Vomiting	173.75	22.48	323	10854	665505	79067706
Desmoplastic small round cell tumour	130.40	22.48	21	11156	90	79733121
Mucosal inflammation	117.76	22.48	92	11085	75488	79657723
Diarrhoea	105.26	22.48	315	10862	880174	78853037
Lower respiratory tract infection	105.12	22.48	109	11068	129111	79604100
Skin candida	104.63	22.48	29	11148	2058	79731153
Pituitary tumour benign	98.59	22.48	29	11148	2547	79730664
Constipation	80.51	22.48	143	11034	282907	79450304
Ejection fraction decreased	76.34	22.48	52	11125	34525	79698686
Metastases to peritoneum	72.09	22.48	26	11151	4346	79728865
Hyperprolactinaemia	66.72	22.48	25	11152	4651	79728560
Neuropathy peripheral	66.27	22.48	90	11087	141215	79591996
Hypomagnesaemia	62.20	22.48	52	11125	46859	79686352
Mouth ulceration	60.32	22.48	47	11130	38347	79694864
Lacrimation increased	59.83	22.48	38	11139	22439	79710772
Abdominal pain	53.57	22.48	147	11030	389422	79343789
Excessive eye blinking	51.55	22.48	16	11161	1685	79731526
Nail dystrophy	50.43	22.48	14	11163	999	79732212
Metastases to lymph nodes	50.40	22.48	26	11151	10371	79722840
Secondary adrenocortical insufficiency	46.25	22.48	17	11160	2997	79730214
Lethargy	44.65	22.48	56	11121	81236	79651975
Hypokalaemia	43.75	22.48	75	11102	143965	79589246
Nail infection	42.32	22.48	15	11162	2384	79730827
Metastases to liver	40.90	22.48	33	11144	28281	79704930
Anaphylactic reaction	40.23	22.48	54	11123	83689	79649522
Rectal cancer metastatic	40.17	22.48	10	11167	466	79732745
Vaginal discharge	40.08	22.48	20	11157	7443	79725768
Bone pain	39.92	22.48	44	11133	55698	79677513
Poor peripheral circulation	39.47	22.48	16	11161	3667	79729544
Perforation	37.35	22.48	12	11165	1414	79731797
Axillary pain	36.25	22.48	13	11164	2136	79731075
Dystonia	35.36	22.48	27	11150	21372	79711839
Liver function test abnormal	34.74	22.48	44	11133	64431	79668780
Febrile neutropenia	34.54	22.48	90	11087	230909	79502302
Drug ineffective	33.58	22.48	63	11114	1080850	78652361
Overflow diarrhoea	32.72	22.48	7	11170	165	79733046
Nervous system disorder	31.98	22.48	28	11149	26828	79706383
Pain	31.97	22.48	31	11146	703771	79029440
Vaginal cellulitis	30.43	22.48	6	11171	93	79733118
Sepsis	29.63	22.48	94	11083	269334	79463877
Abnormal loss of weight	29.62	22.48	17	11160	8359	79724852
Ascites	29.31	22.48	44	11133	75518	79657693
Naevus haemorrhage	28.76	22.48	6	11171	125	79733086
Seizure	28.65	22.48	74	11103	188760	79544451
Bruxism	28.35	22.48	13	11164	4013	79729198
Nausea	26.93	22.48	227	10950	956969	78776242
Disease progression	26.70	22.48	71	11106	184291	79548920
Pyrexia	26.48	22.48	174	11003	678535	79054676
Drug hypersensitivity	26.33	22.48	5	11172	298911	79434300
Neutrophil count decreased	26.02	22.48	47	11130	93912	79639299
Acquired cystic kidney disease	25.90	22.48	5	11172	69	79733142
Muscle twitching	25.90	22.48	24	11153	24740	79708471
Catheter site haemorrhage	25.39	22.48	13	11164	5104	79728107
Candida infection	25.36	22.48	29	11148	38185	79695026
Biliary sepsis	24.37	22.48	9	11168	1608	79731603
Hiccups	24.33	22.48	16	11161	10015	79723196
Genital rash	24.28	22.48	8	11169	1020	79732191
Completed suicide	24.17	22.48	3	11174	245764	79487447
Petit mal epilepsy	24.01	22.48	13	11164	5714	79727497
Palpitations	23.90	22.48	54	11123	126556	79606655

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
155017	RXNORM
4018771	VANDF
4018772	VANDF
4019698	VANDF
C0010547	UMLSCUI
CHEBI:3994	CHEBI
CHEMBL648	ChEMBL_ID
DB01176	DRUGBANK_ID
CHEMBL1200497	ChEMBL_ID
D003501	MESH_DESCRIPTOR_UI
6726	PUBCHEM_CID
7151	IUPHAR_LIGAND_ID
176	INN_ID
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
CHEMBL1324714	ChEMBL_ID

Pharmaceutical products:

None