brotizolam ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
diazepam derivatives 409 57801-81-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • brotizolam
  • mederantil
  • lendorm
  • Molecular weight: 393.69
  • Formula: C15H10BrClN4S
  • CLOGP: 2.86
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 0
  • TPSA: 43.07
  • ALOGS: -3.83
  • ROTB: 1

Drug dosage:

DoseUnitRoute
0.25 mg O

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.01 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ
BA (Bioavailability) 70 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.75 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.09 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 4.80 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 0.01 mg/mL Bocci G, Oprea TI, Benet LZ

Approvals:

DateAgencyCompanyOrphan
Jan. 1, 1983 YEAR INTRODUCED

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
Hepatic function abnormal 109.10 18.48 60 6494 37082 63445386
Altered state of consciousness 97.56 18.48 49 6505 25181 63457287
Platelet count decreased 84.20 18.48 80 6474 116042 63366426
Interstitial lung disease 69.96 18.48 55 6499 61853 63420615
Decreased appetite 66.90 18.48 104 6450 250948 63231520
Neutrophil count decreased 65.65 18.48 51 6503 56355 63426113
Anaemia 65.26 18.48 112 6442 293318 63189150
Distributive shock 64.42 18.48 17 6537 1366 63481102
Suicide attempt 62.19 18.48 51 6503 60867 63421601
Sopor 60.12 18.48 34 6520 22130 63460338
Cardiac failure 58.16 18.48 58 6496 89084 63393384
Fatigue 57.85 18.48 11 6543 888017 62594451
Malignant catatonia 51.86 18.48 10 6544 190 63482278
Drug ineffective 46.84 18.48 25 6529 1044740 62437728
Drug abuse 43.31 18.48 45 6509 72473 63409995
Drug eruption 42.48 18.48 30 6524 28664 63453804
Gamma-glutamyltransferase increased 37.91 18.48 30 6524 34001 63448467
Cerebral infarction 37.75 18.48 26 6528 23867 63458601
Iron deficiency anaemia 37.01 18.48 24 6530 19945 63462523
Neuroleptic malignant syndrome 34.06 18.48 19 6535 12037 63470431
White blood cell count decreased 32.01 18.48 54 6500 139050 63343418
Erythema multiforme 31.41 18.48 17 6537 10152 63472316
Overdose 29.61 18.48 47 6507 115031 63367437
Osteonecrosis of jaw 28.89 18.48 26 6528 35097 63447371
Malignant neoplasm progression 27.55 18.48 38 6516 82083 63400385
Intentional overdose 27.45 18.48 36 6518 74116 63408352
Pain 27.28 18.48 22 6532 740606 62741862
Lymphocyte count decreased 26.07 18.48 23 6531 30234 63452234
Alopecia 24.57 18.48 3 6551 337533 63144935
Pyrexia 23.99 18.48 104 6450 470374 63012094
Renal impairment 23.99 18.48 37 6517 88318 63394150
Febrile neutropenia 23.37 18.48 43 6511 118406 63364062
Vasoplegia syndrome 22.74 18.48 8 6546 1691 63480777
Lip erosion 22.67 18.48 7 6547 986 63481482
Hyponatraemia 22.56 18.48 41 6513 111859 63370609
Bradyphrenia 22.48 18.48 12 6542 6968 63475500
Oromandibular dystonia 22.28 18.48 6 6548 521 63481947
Hypokalaemia 22.16 18.48 39 6515 103765 63378703
Drug withdrawal syndrome neonatal 21.16 18.48 8 6546 2073 63480395
Hepatocellular carcinoma 20.75 18.48 8 6546 2186 63480282
Hypersensitivity 20.34 18.48 3 6551 292682 63189786
Psychiatric symptom 19.75 18.48 10 6544 5213 63477255
Intracranial pressure increased 19.74 18.48 10 6544 5217 63477251
Concomitant disease aggravated 19.50 18.48 12 6542 9100 63473368
Dyskinesia 19.34 18.48 20 6534 31982 63450486
Rhabdomyolysis 18.90 18.48 23 6531 43928 63438540
Swelling 18.73 18.48 3 6551 275375 63207093

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
Hepatic function abnormal 105.04 18.46 78 6499 44285 34906069
Altered state of consciousness 87.05 18.46 54 6523 22839 34927515
Interstitial lung disease 84.43 18.46 81 6496 65201 34885153
Platelet count decreased 46.75 18.46 82 6495 119635 34830719
Pneumonia aspiration 44.91 18.46 47 6530 41856 34908498
Suicide attempt 42.14 18.46 44 6533 39072 34911282
Decreased appetite 37.68 18.46 91 6486 166301 34784053
Fatigue 35.15 18.46 13 6564 370640 34579714
Neutrophil count decreased 34.16 18.46 45 6532 51059 34899295
Renal impairment 32.12 18.46 61 6516 94452 34855902
Drug ineffective 31.62 18.46 24 6553 456727 34493627
Drug eruption 30.13 18.46 27 6550 19871 34930483
Disseminated intravascular coagulation 29.91 18.46 28 6549 21788 34928566
Blood creatine phosphokinase increased 29.21 18.46 39 6538 44818 34905536
Hyperuricaemia 28.10 18.46 18 6559 8025 34942329
Liver disorder 25.11 18.46 31 6546 32966 34917388
Pyrexia 24.99 18.46 126 6451 332887 34617467
Hypoglycaemia 23.34 18.46 39 6538 54601 34895753
Enterocolitis 23.29 18.46 16 6561 8010 34942344
Pneumonia 22.99 18.46 131 6446 362496 34587858
Cardiac failure 22.89 18.46 52 6525 91196 34859158
Cerebral infarction 22.86 18.46 27 6550 27428 34922926
White blood cell count increased 19.79 18.46 31 6546 41120 34909234
Asthenia 19.47 18.46 11 6566 245240 34705114
Malignant neoplasm progression 18.65 18.46 47 6530 87999 34862355

FDA Adverse Event Reporting System (Geriatric)

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
Hepatic function abnormal 200.75 16.17 135 13340 72972 79657941
Altered state of consciousness 175.90 16.17 103 13372 43719 79687194
Interstitial lung disease 137.38 16.17 129 13346 112471 79618442
Platelet count decreased 128.19 16.17 161 13314 194503 79536410
Suicide attempt 97.26 16.17 93 13382 82839 79648074
Decreased appetite 95.62 16.17 191 13284 342227 79388686
Neutrophil count decreased 94.68 16.17 97 13378 93862 79637051
Fatigue 90.58 16.17 23 13452 929704 78801209
Drug ineffective 72.54 16.17 47 13428 1080866 78650047
Anaemia 70.44 16.17 199 13276 444816 79286097
Cardiac failure 68.70 16.17 106 13369 154736 79576177
Drug eruption 64.67 16.17 56 13419 43879 79687034
Pneumonia aspiration 61.81 16.17 66 13409 66901 79664012
Cerebral infarction 58.85 16.17 54 13421 45622 79685291
Sopor 58.81 16.17 47 13428 32963 79697950
White blood cell count decreased 51.19 16.17 104 13371 188184 79542729
Malignant neoplasm progression 48.00 16.17 84 13391 135906 79595007
Renal impairment 47.53 16.17 91 13384 157692 79573221
Gamma-glutamyltransferase increased 45.43 16.17 51 13424 54629 79676284
Neuroleptic malignant syndrome 44.38 16.17 37 13438 27522 79703391
Disseminated intravascular coagulation 43.51 16.17 41 13434 35801 79695112
Pyrexia 41.77 16.17 225 13250 678484 79052429
Distributive shock 41.46 16.17 16 13459 2671 79728242
Pain 38.98 16.17 37 13438 703765 79027148
Lymphocyte count decreased 37.40 16.17 43 13432 47246 79683667
Liver disorder 36.99 16.17 53 13422 72364 79658549
Intentional overdose 35.51 16.17 64 13411 105896 79625017
Concomitant disease aggravated 35.32 16.17 24 13451 13143 79717770
Blood creatine phosphokinase increased 34.68 16.17 49 13426 66041 79664872
Malignant catatonia 33.75 16.17 9 13466 456 79730457
Erythema multiforme 33.30 16.17 26 13449 17625 79713288
Hyperuricaemia 32.83 16.17 22 13453 11777 79719136
Bradyphrenia 32.43 16.17 21 13454 10619 79720294
Upper respiratory tract inflammation 32.06 16.17 15 13460 4020 79726893
Rhabdomyolysis 31.67 16.17 60 13415 103071 79627842
Blood pressure decreased 30.71 16.17 58 13417 99408 79631505
Decubitus ulcer 29.36 16.17 23 13452 15664 79715249
Iron deficiency anaemia 28.57 16.17 28 13447 25644 79705269
Drug hypersensitivity 27.84 16.17 8 13467 298908 79432005
Overdose 27.69 16.17 81 13394 184125 79546788
Osteonecrosis of jaw 27.17 16.17 35 13440 43191 79687722
Asthenia 27.02 16.17 28 13447 511661 79219252
Blood lactate dehydrogenase increased 26.66 16.17 33 13442 39137 79691776
Product dose omission issue 26.26 16.17 5 13470 247532 79483381
Arthralgia 26.22 16.17 35 13440 571768 79159145
White blood cell count increased 26.18 16.17 46 13429 74587 79656326
Subdural haematoma 25.56 16.17 29 13446 31405 79699508
Water intoxication 25.04 16.17 8 13467 766 79730147
Hypersensitivity 24.45 16.17 7 13468 262232 79468681
Enterocolitis 24.44 16.17 20 13455 14492 79716421
Hypokalaemia 24.24 16.17 66 13409 143974 79586939
Restlessness 23.69 16.17 34 13441 46458 79684455
Pneumonia 23.50 16.17 191 13284 660055 79070858
Febrile neutropenia 23.48 16.17 89 13386 230910 79500003
Hypoglycaemia 22.84 16.17 52 13423 101542 79629371
Confusional state 22.35 16.17 13 13462 317984 79412929
Alopecia 21.89 16.17 6 13469 231349 79499564
Swelling 21.70 16.17 5 13470 216706 79514207
Loss of consciousness 21.64 16.17 70 13405 167873 79563040
Fibrin degradation products increased 21.12 16.17 6 13469 385 79730528
Hyponatraemia 21.03 16.17 72 13403 177776 79553137
Salivary hypersecretion 20.65 16.17 18 13457 14206 79716707
Radiation pneumonitis 20.54 16.17 11 13464 3922 79726991
Rheumatoid arthritis 20.50 16.17 5 13470 208465 79522448
Peripheral swelling 20.44 16.17 10 13465 269607 79461306
Embolic stroke 20.36 16.17 14 13461 7812 79723101
Paraesthesia 19.93 16.17 3 13472 176320 79554593
Hypokinesia 19.75 16.17 20 13455 19040 79711873
Pneumonia bacterial 19.52 16.17 20 13455 19311 79711602
Psychiatric symptom 19.29 16.17 13 13462 7022 79723891
Skin erosion 19.28 16.17 11 13464 4434 79726479
Dyskinesia 18.91 16.17 30 13445 44743 79686170
Oromandibular dystonia 18.85 16.17 7 13468 1051 79729862
Constipation 18.80 16.17 96 13379 282954 79447959
Pleural effusion 18.22 16.17 60 13415 145202 79585711
Cholangitis 18.21 16.17 16 13459 12760 79718153
Dyspnoea 18.10 16.17 79 13396 856946 78873967
Aspartate aminotransferase increased 18.05 16.17 58 13417 138583 79592330
Hypoalbuminaemia 17.91 16.17 20 13455 21277 79709636
Delirium 17.58 16.17 42 13433 84585 79646328
Femoral neck fracture 17.32 16.17 14 13461 9970 79720943
Drug-induced liver injury 17.32 16.17 36 13439 66081 79664832
Aortic dissection 17.22 16.17 10 13465 4165 79726748
Pharyngitis 17.11 16.17 20 13455 22355 79708558
Infusion related reaction 16.76 16.17 9 13466 230228 79500685
Lip erosion 16.22 16.17 7 13468 1553 79729360

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N05CD09 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Benzodiazepine derivatives
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D006993 Hypnotics and Sedatives

Drug Use | Suggest Off label Use Form| |View source of the data|

None




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.34 Basic
pKa2 4.87 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
Platelet-activating factor receptor GPCR IC50 6.52 CHEMBL

External reference:

IDSource
D01744 KEGG_DRUG
19790 RXNORM
C0054151 UMLSCUI
CHEBI:31308 CHEBI
CHEMBL32479 ChEMBL_ID
DB09017 DRUGBANK_ID
C020960 MESH_SUPPLEMENTAL_RECORD_UI
2451 PUBCHEM_CID
4549 INN_ID
5XZM1R3DKF UNII
698050003 SNOMEDCT_US
004151 NDDF

Pharmaceutical products:

None