Scroll

zopiclone Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
hypnotic tranquillizers	2873	43200-80-2

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: zopiclone zimovane imovane	S(+)-enantiomer of racemic zopiclone; azabicyclo(4.3.0)nonane; a nonbenzodiazepine; one of the so-called of Z drugs (zopiclone, eszopiclone, zolpidem, and zaleplon) for which there is some correlation with tumors; was term of zopiclone 2004-2007 Molecular weight: 388.81 Formula: C17H17ClN6O3 CLOGP: 1.25 LIPINSKI: 0 HAC: 9 HDO: 0 TPSA: 91.76 ALOGS: -2.64 ROTB: 3

Molecule

Description

Molfile Inchi Smiles

Synonyms:

zopiclone
zimovane
imovane

S(+)-enantiomer of racemic zopiclone; azabicyclo(4.3.0)nonane; a nonbenzodiazepine; one of the so-called of Z drugs (zopiclone, eszopiclone, zolpidem, and zaleplon) for which there is some correlation with tumors; was term of zopiclone 2004-2007

Molecular weight: 388.81
Formula: C17H17ClN6O3
CLOGP: 1.25
LIPINSKI: 0
HAC: 9
HDO: 0
TPSA: 91.76
ALOGS: -2.64
ROTB: 3

Drug dosage:

Dose	Unit	Route
7.50	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.12 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	4.50 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.28 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	1.30 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	3.30 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.20 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	5.20 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Dec. 15, 2004	FDA	SUNOVION PHARMS INC

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
Toxicity to various agents	1379.15	39.68	387	1936	32367	2323395
Coma	1077.40	39.68	247	2076	8809	2346953
Intentional overdose	788.84	39.68	201	2122	11120	2344642
Somnolence	733.72	39.68	222	2101	23263	2332499
Fall	604.10	39.68	228	2095	46871	2308891
Pneumonia aspiration	544.86	39.68	121	2202	3621	2352141
Suicide attempt	534.67	39.68	148	2175	11134	2344628
Overdose	447.66	39.68	147	2176	19760	2336002
Confusional state	324.58	39.68	122	2201	24222	2331540
Hypotension	277.19	39.68	118	2205	32318	2323444
Electrocardiogram QT prolonged	276.96	39.68	82	2241	7732	2348030
Depressed level of consciousness	257.27	39.68	77	2246	7527	2348235
Drug dependence	249.86	39.68	62	2261	2983	2352779
Drug abuse	238.21	39.68	81	2242	11945	2343817
Intentional self-injury	217.03	39.68	59	2264	4068	2351694
Poisoning deliberate	214.53	39.68	46	2277	1145	2354617
Gastrooesophageal reflux disease	210.80	39.68	69	2254	9026	2346736
Orthostatic hypotension	188.61	39.68	49	2274	2830	2352932
Completed suicide	180.69	39.68	77	2246	20957	2334805
Altered state of consciousness	174.37	39.68	49	2274	3811	2351951
Prescription form tampering	152.47	39.68	25	2298	128	2355634
Loss of consciousness	145.65	39.68	64	2259	18703	2337059
Tachycardia	140.53	39.68	60	2263	16349	2339413
Hypokalaemia	121.99	39.68	48	2275	10606	2345156
Mydriasis	113.14	39.68	31	2292	2188	2353574
Hyponatraemia	111.61	39.68	48	2275	13277	2342485
Hypersensitivity vasculitis	99.09	39.68	25	2298	1277	2354485
Somnambulism	97.95	39.68	23	2300	867	2354895
Hypotonia	96.74	39.68	26	2297	1704	2354058
Malaise	96.55	39.68	71	2252	55514	2300248
Hypothermia	95.69	39.68	27	2296	2121	2353641
Acute kidney injury	93.40	39.68	54	2269	28068	2327694
Agitation	93.13	39.68	40	2283	11011	2344751
Hepatocellular injury	90.67	39.68	30	2293	4025	2351737
Bradycardia	90.31	39.68	38	2285	9943	2345819
Drug reaction with eosinophilia and systemic symptoms	89.09	39.68	32	2291	5486	2350276
Rhabdomyolysis	86.61	39.68	33	2290	6671	2349091
Asphyxia	85.00	39.68	21	2302	983	2354779
Disturbance in attention	84.44	39.68	31	2292	5654	2350108
Hallucination	83.79	39.68	34	2289	8114	2347648
Foetal exposure during pregnancy	83.07	39.68	30	2293	5222	2350540
Hallucination, visual	82.78	39.68	26	2297	2953	2352809
Dysarthria	81.33	39.68	31	2292	6271	2349491
Bezoar	78.84	39.68	15	2308	198	2355564
Lung disorder	78.16	39.68	30	2293	6182	2349580
Blood creatine phosphokinase increased	76.24	39.68	28	2295	5108	2350654
Suicidal ideation	73.71	39.68	34	2289	11053	2344709
Hypoglycaemia	72.67	39.68	31	2292	8376	2347386
Sinus tachycardia	71.92	39.68	24	2299	3301	2352461
Balance disorder	71.45	39.68	32	2291	9715	2346047
Abdominal pain	71.29	39.68	49	2274	34325	2321437
Miosis	71.28	39.68	19	2304	1205	2354557
Exposure during pregnancy	69.55	39.68	43	2280	25176	2330586
Cholestasis	69.27	39.68	24	2299	3697	2352065
Anxiety	68.41	39.68	45	2278	29314	2326448
Dehydration	66.56	39.68	40	2283	22255	2333507
Intentional product misuse	65.89	39.68	30	2293	9459	2346303
Circulatory collapse	65.43	39.68	23	2300	3697	2352065
Shock	63.78	39.68	23	2300	3981	2351781
Bradypnoea	62.68	39.68	14	2309	420	2355342
Lethargy	61.87	39.68	28	2295	8702	2347060
Agitation neonatal	61.76	39.68	11	2312	98	2355664
Eczema	60.93	39.68	21	2302	3184	2352578
Panic attack	60.30	39.68	22	2301	3934	2351828
Extrapyramidal disorder	59.06	39.68	19	2304	2328	2353434
Tremor	58.90	39.68	36	2287	20625	2335137
Maternal exposure during pregnancy	58.64	39.68	32	2291	14831	2340931
Interstitial lung disease	58.36	39.68	26	2297	7786	2347976
Hyperhidrosis	57.53	39.68	32	2291	15390	2340372
Disorientation	56.72	39.68	24	2299	6348	2349414
Antipsychotic drug level above therapeutic	55.83	39.68	11	2312	176	2355586
Agranulocytosis	55.44	39.68	20	2303	3462	2352300
Foetal death	54.40	39.68	17	2306	1895	2353867
Delirium	54.36	39.68	22	2301	5201	2350561
Aggression	52.72	39.68	21	2302	4765	2350997
Nausea	52.62	39.68	70	2253	112119	2243643
Hallucination, auditory	52.12	39.68	17	2306	2175	2353587
Diarrhoea	51.77	39.68	60	2263	83504	2272258
Rash maculo-papular	51.55	39.68	20	2303	4232	2351530
Cardio-respiratory arrest	51.41	39.68	25	2298	9121	2346641
Analgesic drug level increased	50.94	39.68	11	2312	281	2355481
Urinary retention	50.76	39.68	19	2304	3648	2352114
Distributive shock	50.05	39.68	9	2314	85	2355677
Developmental hip dysplasia	49.70	39.68	10	2313	179	2355583
Urinary tract infection	49.00	39.68	37	2286	29905	2325857
Sputum discoloured	48.95	39.68	14	2309	1152	2354610
Cardiac arrest	47.68	39.68	28	2295	14902	2340860
Depression	46.55	39.68	35	2288	28097	2327665
Blood pressure decreased	45.26	39.68	23	2300	9213	2346549
Inappropriate antidiuretic hormone secretion	43.37	39.68	15	2308	2294	2353468
Ear haemorrhage	42.79	39.68	9	2314	202	2355560
Diabetic hyperosmolar coma	42.37	39.68	8	2315	101	2355661
Sedation	41.41	39.68	16	2307	3346	2352416
Muscle twitching	40.73	39.68	15	2308	2750	2353012

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
Toxicity to various agents	744.02	48.58	245	1440	28896	1716200
Coma	634.06	48.58	160	1525	7102	1737994
Somnolence	444.16	48.58	146	1539	16593	1728503
Confusional state	413.64	48.58	147	1538	21131	1723965
Intentional overdose	410.24	48.58	115	1570	7555	1737541
Overdose	337.45	48.58	119	1566	16582	1728514
Poisoning deliberate	336.86	48.58	65	1620	777	1744319
Fall	325.37	48.58	132	1553	27082	1718014
Drug dependence	252.77	48.58	66	1619	3261	1741835
Suicide attempt	250.43	48.58	78	1607	7303	1737793
Drug abuse	178.36	48.58	71	1614	13618	1731478
Prescription form tampering	168.03	48.58	28	1657	130	1744966
Hypotension	156.83	48.58	82	1603	29572	1715524
Hepatocellular injury	147.40	48.58	43	1642	3188	1741908
Completed suicide	143.41	48.58	64	1621	16248	1728848
Acute kidney injury	136.11	48.58	79	1606	34865	1710231
Agitation	122.18	48.58	51	1634	10975	1734121
Cholestasis	120.84	48.58	38	1647	3627	1741469
Bradycardia	117.63	48.58	49	1636	10485	1734611
Rhabdomyolysis	111.87	48.58	48	1637	11042	1734054
Pneumonia aspiration	111.15	48.58	39	1646	5227	1739869
Electrocardiogram QT prolonged	109.18	48.58	39	1646	5506	1739590
Drug interaction	100.17	48.58	60	1625	27898	1717198
Tachycardia	99.57	48.58	46	1639	12582	1732514
Metabolic acidosis	98.86	48.58	36	1649	5366	1739730
Intentional product misuse	98.44	48.58	39	1646	7319	1737777
Alcohol poisoning	95.31	48.58	21	1664	491	1744605
Hypothermia	91.85	48.58	26	1659	1722	1743374
Hyperkalaemia	89.44	48.58	38	1647	8509	1736587
Hypoglycaemia	83.29	48.58	36	1649	8402	1736694
Insomnia	82.76	48.58	44	1641	16232	1728864
Miosis	82.26	48.58	23	1662	1455	1743641
Depression	81.78	48.58	44	1641	16625	1728471
Withdrawal syndrome	80.70	48.58	25	1660	2263	1742833
Bradypnoea	74.93	48.58	16	1669	321	1744775
Altered state of consciousness	74.10	48.58	26	1659	3471	1741625
Macrophages increased	71.38	48.58	10	1675	8	1745088
Neuroleptic malignant syndrome	68.98	48.58	24	1661	3124	1741972
Intentional self-injury	68.83	48.58	23	1662	2650	1742446
Hepatitis	65.28	48.58	26	1659	4929	1740167
Lactic acidosis	60.97	48.58	25	1660	5104	1739992
Death	58.27	48.58	71	1614	87372	1657724
Respiratory distress	57.46	48.58	24	1661	5133	1739963
Cardiomegaly	55.80	48.58	19	1666	2315	1742781
Coma scale abnormal	55.68	48.58	14	1671	585	1744511
Dysarthria	53.68	48.58	23	1662	5236	1739860
Foetal alcohol syndrome	53.35	48.58	8	1677	15	1745081
Substance abuse	53.02	48.58	15	1670	988	1744108
Thrombocytopenia	52.08	48.58	36	1649	21213	1723883
Balance disorder	51.47	48.58	23	1662	5789	1739307
Blood ethanol increased	50.95	48.58	9	1676	62	1745034
Dextrocardia	50.23	48.58	8	1677	26	1745070
Pulmonary oedema	48.71	48.58	23	1662	6563	1738533
Depressed level of consciousness	48.69	48.58	23	1662	6569	1738527

Pharmacologic Action:

Source	Code	Description
ATC	N05CF01	NERVOUS SYSTEM PSYCHOLEPTICS HYPNOTICS AND SEDATIVES Benzodiazepine related drugs
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D002492	Central Nervous System Depressants
MeSH PA	D006993	Hypnotics and Sedatives
CHEBI has role	CHEBI:35488	central nervous system depressant
CHEBI has role	CHEBI:35717	sedative

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID
Insomnia	indication	193462001
Suicidal thoughts	contraindication	6471006
Asthenia	contraindication	13791008
Alcohol intoxication	contraindication	25702006
Depressive disorder	contraindication	35489007
Hepatic failure	contraindication	59927004
Sleep automatism	contraindication	247962006
Severe chronic obstructive pulmonary disease	contraindication	313299006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	7.95	Basic
pKa2	2.26	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
GABA-A receptor alpha-5/beta-3/gamma-2	Ion channel	P18507 P28472 P31644	GBRA5_HUMAN GBRB3_HUMAN GBRG2_HUMAN	POSITIVE MODULATOR	Ki	7.28	WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-3/beta-2/gamma-2	Ion channel	P18507 P34903 P47870	GBRA3_HUMAN GBRB2_HUMAN GBRG2_HUMAN	POSITIVE MODULATOR	Ki	6.58	WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-3/beta-2/gamma-3	Ion channel	P34903 P47870 Q99928	GBRA3_HUMAN GBRB2_HUMAN GBRG3_HUMAN	POSITIVE MODULATOR	Ki	6.49	WOMBAT-PK	DRUG LABEL
GABA-A receptor alpha-1/beta-2/gamma-3	Ion channel	P14867 P47870 Q99928	GBRA1_HUMAN GBRB2_HUMAN GBRG3_HUMAN	POSITIVE MODULATOR	Ki	7.15	WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-5/beta-2/gamma-2	Ion channel	P18507 P31644 P47870	GBRA5_HUMAN GBRB2_HUMAN GBRG2_HUMAN	POSITIVE MODULATOR	Ki	7.28	WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-5/beta-2/gamma-3	Ion channel	P31644 P47870 Q99928	GBRA5_HUMAN GBRB2_HUMAN GBRG3_HUMAN	POSITIVE MODULATOR	Ki	6.75	WOMBAT-PK	DRUG LABEL
GABA-A receptor alpha-1/beta-2/gamma-2	Ion channel	P14867 P18507 P47870	GBRA1_HUMAN GBRB2_HUMAN GBRG2_HUMAN	POSITIVE MODULATOR	Ki	7.18	WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-5/beta-3/gamma-3	Ion channel	P28472 P31644 Q99928	GBRA5_HUMAN GBRB3_HUMAN GBRG3_HUMAN	POSITIVE MODULATOR	Ki	6.75	WOMBAT-PK	DRUG LABEL
GABA-A receptor; anion channel	Ion channel		GBRA1_RAT GBRA2_RAT GBRA3_RAT GBRA4_RAT GBRA5_RAT GBRA6_RAT GBRB1_RAT GBRB2_RAT GBRB3_RAT GBRD_RAT GBRE_RAT GBRG1_RAT GBRG2_RAT GBRG3_RAT GBRP_RAT Q91ZM7_RAT		IC50	7.54	CHEMBL

External reference:

ID	Source
C0078847	UMLSCUI
D01372	KEGG_DRUG
03A5ORL08Q	UNII
4462	INN_ID
321174005	SNOMEDCT_US
003775	NDDF
40001	RXNORM
395929002	SNOMEDCT_US
CHEMBL135400	ChEMBL_ID
DB01198	DRUGBANK_ID
CHEBI:32315	CHEBI
5735	PUBCHEM_CID
7430	IUPHAR_LIGAND_ID
C515050	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

None