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cyclizine 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	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 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	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:

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	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)

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

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
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