brotizolam 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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 µM/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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.001 Moderate 0.69
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.855 Moderate 0.69
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 55.976 10^-6 cm/s Moderate 0.69
dh-clint Dog hepatocyte intrinsic clearance 21.878 uL/min/10^6 cells Moderate 0.69
dppb Dog plasma protein binding (% unbound) 5.560 % Moderate 0.69
fcs-ppb Fetal calf serum protein binding (% unbound) 19.100 % Moderate 0.69
herg hERG pIC50 4.826 pIC50 Moderate 0.69
hh-clint Human hepatocyte intrinsic clearance 9.840 uL/min/10^6 cells Moderate 0.69
hlm-clint Human liver microsomal intrinsic clearance 28.774 uL/min/mg protein Moderate 0.69
hppb Human plasma protein binding (% unbound) 6.050 % Moderate 0.69
kinase-safety-class ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,GRK2,GSK3B,ITK,MAPK10,MAPK7,MAPK9,MET,PDK1,PDK4,PDPK1,PIK3CB,PIK3CD,PIK3CG,PRKDC,STK33,TEK,TTK 28
kinase-selectivity-class GRK2 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.679 Moderate 0.69
mh-clint Mouse hepatocyte intrinsic clearance 55.081 Moderate 0.69
mppb Mouse plasma protein binding (% unbound) 7.020 Moderate 0.69
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 9.616 Moderate 0.69
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 11.390 % Moderate 0.69
rh-clint Rat hepatocyte intrinsic clearance 97.724 uL/min/10^6 cells Moderate 0.69
rh-fuinc Rat hepatocyte fraction unbound in incubation 43.760 % Moderate 0.69
rppb Rat plasma protein binding (% unbound) 5.450 % Moderate 0.69
solubility-dd Solubility at pH 7.4 in DMSO 76.384 uM Moderate 0.69

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
Altered state of consciousness 136.64 21.20 63 7923 31469 90588992
Hepatic function abnormal 130.50 21.20 69 7917 46219 90574242
Platelet count decreased 103.27 21.20 90 7896 136879 90483582
Suicide attempt 92.40 21.20 66 7920 75333 90545128
Interstitial lung disease 82.58 21.20 62 7924 76343 90544118
Neutrophil count decreased 77.20 21.20 58 7928 71474 90548987
Intentional overdose 73.39 21.20 63 7923 93771 90526690
Anaemia 68.29 21.20 116 7870 352686 90267775
Cardiac failure 63.16 21.20 62 7924 109434 90511027
Fatigue 62.45 21.20 13 7973 1154010 89466451
Sopor 61.77 21.20 34 7952 24610 90595851
Distributive shock 55.92 21.20 18 7968 3406 90617055
Gamma-glutamyltransferase increased 55.35 21.20 37 7949 37915 90582546
Decreased appetite 54.19 21.20 109 7877 376431 90244030
Drug eruption 52.80 21.20 35 7951 35372 90585089
Drug abuse 51.95 21.20 49 7937 82298 90538163
Malignant catatonia 51.78 21.20 10 7976 226 90620235
Cerebral infarction 51.45 21.20 31 7955 26565 90593896
Drug ineffective 47.67 21.20 32 7954 1384266 89236195
Iron deficiency anaemia 46.86 21.20 28 7958 23634 90596827
Overdose 43.27 21.20 61 7925 157648 90462813
Osteonecrosis of jaw 36.26 21.20 29 7957 39074 90581387
Neuroleptic malignant syndrome 35.56 21.20 20 7966 15076 90605385
White blood cell count decreased 34.99 21.20 57 7929 167052 90453409
Intracranial pressure increased 33.89 21.20 15 7971 6796 90613665
Erythema multiforme 33.75 21.20 18 7968 12228 90608233
Malignant neoplasm progression 33.33 21.20 44 7942 106826 90513635
Hepatic encephalopathy 31.77 21.20 18 7968 13754 90606707
Blood bilirubin increased 31.57 21.20 28 7958 43442 90577019
Renal impairment 30.73 21.20 42 7944 105379 90515082
Lymphocyte count decreased 30.40 21.20 25 7961 35025 90585436
Alopecia 30.17 21.20 4 7982 495067 90125394
Pyrexia 28.27 21.20 124 7862 660361 89960100
Pain 28.02 21.20 28 7958 996313 89624148
Hypersensitivity 26.93 21.20 4 7982 454673 90165788
Swelling 26.47 21.20 3 7983 419055 90201406
Depressed level of consciousness 25.89 21.20 32 7954 72752 90547709
Rhabdomyolysis 25.83 21.20 27 7959 51229 90569232
Hepatocellular carcinoma 24.87 21.20 9 7977 2419 90618042
Hyponatraemia 24.55 21.20 43 7943 133495 90486966
Urea cycle disorder 23.85 21.20 4 7982 39 90620422
Bradyphrenia 23.29 21.20 12 7974 7600 90612861
Vascular device infection 23.29 21.20 14 7972 11938 90608523
Dehydration 22.94 21.20 52 7934 194395 90426066
Pulmonary alveolar haemorrhage 22.93 21.20 11 7975 5987 90614474
Febrile neutropenia 22.89 21.20 46 7940 158303 90462158
Bladder sphincter atony 22.61 21.20 5 7981 223 90620238
Hypokalaemia 22.54 21.20 41 7945 131075 90489386
Oromandibular dystonia 22.42 21.20 6 7980 597 90619864
Lip erosion 22.24 21.20 7 7979 1231 90619230
Blood pressure decreased 22.06 21.20 30 7956 74865 90545596
Hallucination, auditory 21.91 21.20 15 7971 15960 90604501
Infusion related reaction 21.82 21.20 5 7981 416775 90203686
Dyskinesia 21.62 21.20 21 7965 36513 90583948
Drug hypersensitivity 21.58 21.20 7 7979 463602 90156859
Renal tubular acidosis 21.56 21.20 8 7978 2307 90618154
Drug withdrawal syndrome neonatal 21.55 21.20 8 7978 2311 90618150
Peripheral swelling 21.54 21.20 5 7981 413101 90207360

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 118.43 18.03 86 7265 51481 42562503
Interstitial lung disease 88.79 18.03 87 7264 78375 42535609
Altered state of consciousness 86.42 18.03 57 7294 29202 42584782
Pneumonia aspiration 53.76 18.03 54 7297 50024 42563960
Platelet count decreased 48.28 18.03 86 7265 138495 42475489
Suicide attempt 44.57 18.03 47 7304 46053 42567931
Decreased appetite 40.27 18.03 97 7254 193040 42420944
Drug ineffective 39.22 18.03 31 7320 630166 41983818
Blood creatine phosphokinase increased 35.96 18.03 43 7308 48295 42565689
Renal impairment 34.06 18.03 65 7286 110163 42503821
Fatigue 33.10 18.03 17 7334 435624 42178360
Neutrophil count decreased 32.55 18.03 47 7304 63368 42550616
Pneumonia 30.91 18.03 149 7202 422000 42191984
Drug eruption 30.65 18.03 28 7323 23047 42590937
Disseminated intravascular coagulation 28.93 18.03 28 7323 24766 42589218
Pyrexia 28.77 18.03 139 7212 393903 42220081
Cerebral infarction 28.74 18.03 31 7320 31138 42582846
Cardiac failure 28.19 18.03 59 7292 106797 42507187
Liver disorder 27.42 18.03 34 7317 39610 42574374
Foreign body aspiration 26.92 18.03 7 7344 315 42613669
Enterocolitis 26.07 18.03 18 7333 9911 42604073
Hypoglycaemia 25.93 18.03 41 7310 59813 42554171
Hyperuricaemia 24.55 18.03 17 7334 9407 42604577
White blood cell count increased 22.52 18.03 33 7318 45054 42568930
Rhabdomyolysis 20.47 18.03 43 7308 77976 42536008
Asthenia 19.78 18.03 12 7339 280781 42333203
White blood cell count decreased 19.36 18.03 52 7299 110344 42503640
Intentional overdose 19.25 18.03 33 7318 51423 42562561
Loss of consciousness 18.78 18.03 46 7305 92308 42521676

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 239.57 17.55 152 15471 89143 110484533
Altered state of consciousness 211.41 17.55 120 15503 57506 110516170
Interstitial lung disease 156.78 17.55 141 15482 139193 110434483
Platelet count decreased 152.53 17.55 175 15448 230268 110343408
Suicide attempt 129.02 17.55 111 15512 103283 110470393
Neutrophil count decreased 104.81 17.55 106 15517 120835 110452841
Fatigue 91.85 17.55 29 15594 1215929 109357747
Decreased appetite 88.06 17.55 202 15421 475644 110098032
Cardiac failure 83.49 17.55 117 15506 187509 110386167
Cerebral infarction 80.00 17.55 63 15560 51775 110521901
Drug ineffective 79.06 17.55 60 15563 1520480 109053196
Intentional overdose 78.22 17.55 95 15528 132406 110441270
Drug eruption 75.97 17.55 62 15561 53597 110520079
Pneumonia aspiration 75.52 17.55 74 15549 81159 110492517
Anaemia 73.77 17.55 206 15417 546880 110026796
Sopor 62.03 17.55 47 15576 36499 110537177
Gamma-glutamyltransferase increased 59.14 17.55 57 15566 61252 110512424
Renal impairment 57.82 17.55 99 15524 188346 110385330
White blood cell count decreased 57.03 17.55 110 15513 229280 110344396
Pyrexia 52.52 17.55 258 15365 898007 109675669
Malignant neoplasm progression 51.31 17.55 90 15533 174477 110399199
Disseminated intravascular coagulation 48.78 17.55 43 15580 41243 110532433
Neuroleptic malignant syndrome 47.46 17.55 39 15584 34020 110539656
Blood creatine phosphokinase increased 45.73 17.55 54 15569 73023 110500653
Overdose 45.07 17.55 101 15522 233693 110339983
Pain 44.18 17.55 42 15581 954913 109618763
Lymphocyte count decreased 42.10 17.55 46 15577 57197 110516479
Rhabdomyolysis 41.94 17.55 67 15556 120334 110453342
Blood pressure decreased 40.03 17.55 64 15559 115027 110458649
Drug hypersensitivity 39.60 17.55 8 15615 454082 110119594
Iron deficiency anaemia 37.54 17.55 33 15590 31526 110542150
Malignant catatonia 36.18 17.55 10 15613 696 110572980
Loss of consciousness 35.82 17.55 83 15540 196223 110377453
Erythema multiforme 35.50 17.55 27 15596 21070 110552606
Arthralgia 35.20 17.55 35 15588 779597 109794079
Distributive shock 35.09 17.55 17 15606 5887 110567789
Hyperuricaemia 34.64 17.55 23 15600 14508 110559168
Concomitant disease aggravated 34.49 17.55 24 15599 16340 110557336
Osteonecrosis of jaw 34.29 17.55 38 15585 47979 110525697
Bradyphrenia 34.00 17.55 21 15602 11707 110561969
Upper respiratory tract inflammation 33.48 17.55 15 15608 4356 110569320
Subdural haematoma 33.47 17.55 33 15590 36421 110537255
Blood lactate dehydrogenase increased 33.25 17.55 36 15587 44298 110529378
Swelling 33.18 17.55 5 15618 351036 110222640
Hypoglycaemia 32.99 17.55 59 15564 116045 110457631
Hypersensitivity 31.52 17.55 9 15614 403989 110169687
Decubitus ulcer 29.94 17.55 23 15600 18213 110555463
Peripheral swelling 29.73 17.55 10 15613 404024 110169652
Product dose omission issue 29.47 17.55 5 15618 321777 110251899
Pneumonia 29.40 17.55 218 15405 876496 109697180
Foreign body aspiration 29.37 17.55 8 15615 527 110573149
Confusional state 29.02 17.55 15 15608 468665 110105011
Water intoxication 28.90 17.55 9 15614 950 110572726
Hypokalaemia 28.84 17.55 73 15550 182375 110391301
Alopecia 28.69 17.55 8 15615 364745 110208931
Hepatic encephalopathy 28.62 17.55 27 15596 28229 110545447
Paraesthesia 28.41 17.55 3 15620 276518 110297158
Febrile neutropenia 27.72 17.55 103 15520 316664 110257012
Restlessness 26.36 17.55 36 15587 56223 110517453
Embolic stroke 26.23 17.55 16 15607 8727 110564949
White blood cell count increased 25.97 17.55 48 15575 96794 110476882
Depressed level of consciousness 25.65 17.55 52 15571 112226 110461450
Infusion related reaction 25.44 17.55 11 15612 381151 110192525
Hepatic enzyme increased 25.30 17.55 7 15616 320885 110252791
Aspartate aminotransferase increased 25.29 17.55 64 15559 159872 110413804
Enterocolitis 24.95 17.55 21 15602 18928 110554748
Liver disorder 24.69 17.55 59 15564 142184 110431492
Pneumonia bacterial 24.53 17.55 24 15599 26237 110547439
Musculoskeletal stiffness 24.23 17.55 5 15618 279817 110293859
Dehydration 23.72 17.55 90 15533 279421 110294255
Skin erosion 23.65 17.55 13 15610 5841 110567835
Femoral neck fracture 23.19 17.55 17 15606 12550 110561126
Systemic lupus erythematosus 23.18 17.55 4 15619 254334 110319342
Pleural effusion 22.95 17.55 66 15557 177643 110396033
Rheumatoid arthritis 22.77 17.55 7 15616 299606 110274070
Hyponatraemia 22.69 17.55 75 15548 217578 110356098
Contraindicated product administered 22.42 17.55 4 15619 248263 110325413
Fibrin degradation products increased 21.52 17.55 6 15617 431 110573245
Immobilisation syndrome 21.37 17.55 7 15616 869 110572807
Cholangitis 21.29 17.55 18 15605 16317 110557359
Dyskinesia 21.25 17.55 31 15592 51415 110522261
Radiation pneumonitis 20.92 17.55 11 15612 4525 110569151
Blood bilirubin increased 20.80 17.55 38 15585 75934 110497742
Hypothyroidism 20.64 17.55 37 15586 72862 110500814
Salivary hypersecretion 20.29 17.55 18 15605 17403 110556273
Constipation 20.25 17.55 102 15521 357684 110215992
Bladder sphincter atony 20.07 17.55 5 15618 232 110573444
Pharyngitis 19.91 17.55 21 15602 25077 110548599
Drug abuse 19.26 17.55 62 15561 177349 110396327
Oromandibular dystonia 19.11 17.55 7 15616 1212 110572464
Sinusitis 19.10 17.55 9 15614 296679 110276997
Drug-induced liver injury 18.92 17.55 48 15575 120019 110453657
Intracranial pressure increased 18.87 17.55 14 15609 10521 110563155
Hypokinesia 18.64 17.55 19 15604 21807 110551869
Muscle spasms 18.59 17.55 8 15615 278149 110295527
Intentional product use issue 18.46 17.55 6 15617 247900 110325776
Cardiac tamponade 17.99 17.55 14 15609 11293 110562383
Dysphagia 17.89 17.55 55 15568 153545 110420131
Renal disorder 17.86 17.55 28 15595 49451 110524225
Haemoglobin decreased 17.82 17.55 76 15547 248651 110325025
Wheezing 17.61 17.55 7 15616 255223 110318453

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
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:35474 anxiolytic drug
CHEBI has role CHEBI:35476 antipsychotic agent
CHEBI has role CHEBI:35623 anticonvulsant
CHEBI has role CHEBI:35717 sedative
CHEBI has role CHEBI:51371 muscle relaxant
CHEBI has role CHEBI:91016 GABA<small><sub>A</sub></small> receptor agonist

Related Drugs by ATC class:

N05CD Benzodiazepine derivatives 14 drugs
cinolazepamdoxefazepamestazolamflunitrazepamflurazepamloprazolamlormetazepammidazolamnimetazepamnitrazepamquazepamremimazolam show all 14 →

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

None




🐶 Veterinary Drug Use

None

🐶 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