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

Stem definitionDrug idCAS RN
hypnotic tranquillizers 2873 43200-80-2

Description:

MoleculeDescription

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:

DoseUnitRoute
7.50 mg O

ADMET properties:

PropertyValueReference
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 ┬ÁM/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:

DateAgencyCompanyOrphan
Dec. 15, 2004 FDA SUNOVION PHARMS INC

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
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 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
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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
GABA-A receptor alpha-5/beta-3/gamma-2 Ion channel POSITIVE MODULATOR Ki 7.28 WOMBAT-PK DRUG LABEL
GABA A receptor alpha-3/beta-2/gamma-2 Ion channel POSITIVE MODULATOR Ki 6.58 WOMBAT-PK DRUG LABEL
GABA A receptor alpha-3/beta-2/gamma-3 Ion channel POSITIVE MODULATOR Ki 6.49 WOMBAT-PK DRUG LABEL
GABA-A receptor alpha-1/beta-2/gamma-3 Ion channel POSITIVE MODULATOR Ki 7.15 WOMBAT-PK DRUG LABEL
GABA A receptor alpha-5/beta-2/gamma-2 Ion channel POSITIVE MODULATOR Ki 7.28 WOMBAT-PK DRUG LABEL
GABA A receptor alpha-5/beta-2/gamma-3 Ion channel POSITIVE MODULATOR Ki 6.75 WOMBAT-PK DRUG LABEL
GABA-A receptor alpha-1/beta-2/gamma-2 Ion channel POSITIVE MODULATOR Ki 7.18 WOMBAT-PK DRUG LABEL
GABA A receptor alpha-5/beta-3/gamma-3 Ion channel POSITIVE MODULATOR Ki 6.75 WOMBAT-PK DRUG LABEL
GABA-A receptor; anion channel Ion channel IC50 7.54 CHEMBL

External reference:

IDSource
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