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

Stem definitionDrug idCAS RN
diazepam derivatives 1202 1622-62-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • flunitrazepam
  • flunidazepam
  • fluridrazepam
  • flunipam
A benzodiazepine with pharmacologic actions similar to those of DIAZEPAM that can cause ANTEROGRADE AMNESIA. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug.
  • Molecular weight: 313.29
  • Formula: C16H12FN3O3
  • CLOGP: 1.78
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 0
  • TPSA: 78.49
  • ALOGS: -4.56
  • ROTB: 2

Drug dosage:

DoseUnitRoute
1 mg O
1 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.00 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) 0.11 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 80 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.90 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.40 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.17 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 25 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.068 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.434 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 96.828 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 52.845 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 26.410 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 44.670 % High 1
herg hERG pIC50 4.568 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 3.648 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 9.954 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 25.790 % High 1
kinase-safety-class ACVR2B,CDK5,EIF2AK3,GRK2,MAPK10,MAPK7,PDK1,PDK2,PDK4,PDPK1,STK33,TTK 12
kinase-selectivity-class AXL,GRK2,PDK4,STK33,TTK 5
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.459 High 1
mh-clint Mouse hepatocyte intrinsic clearance 47.534 High 1
mppb Mouse plasma protein binding (% unbound) 24.660 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.692 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 30.480 % High 1
rh-clint Rat hepatocyte intrinsic clearance 81.846 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 85.480 % High 1
rppb Rat plasma protein binding (% unbound) 24.190 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 344.350 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 1, 1976 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
Overdose 202.89 27.08 116 4506 157593 90466232
Intentional overdose 188.57 27.08 93 4529 93741 90530084
Toxicity to various agents 169.67 27.08 130 4492 287716 90336109
Altered state of consciousness 166.43 27.08 62 4560 31470 90592355
Neuroleptic malignant syndrome 130.94 27.08 43 4579 15053 90608772
Suicide attempt 114.59 27.08 62 4560 75337 90548488
Hepatic function abnormal 102.21 27.08 49 4573 46239 90577586
Salivary hypersecretion 87.37 27.08 28 4594 9064 90614761
Extrapyramidal disorder 74.92 27.08 29 4593 16274 90607551
Loss of consciousness 70.83 27.08 58 4564 140180 90483645
Pneumonia aspiration 65.88 27.08 35 4587 40905 90582920
Psychiatric symptom 60.59 27.08 20 4602 7098 90616727
Blood creatine phosphokinase increased 57.33 27.08 30 4592 33993 90589832
Electrocardiogram QT prolonged 56.74 27.08 39 4583 72417 90551408
Parkinsonism 47.32 27.08 20 4602 14045 90609780
Vasoconstriction 44.06 27.08 10 4612 875 90622950
Drowning 43.50 27.08 9 4613 510 90623315
Hypothermia 42.15 27.08 19 4603 15556 90608269
Stevens-Johnson syndrome 41.37 27.08 23 4599 29353 90594472
Rhabdomyolysis 41.08 27.08 28 4594 51228 90572597
Lymphocytosis 40.53 27.08 12 4610 2985 90620840
Delusion 37.82 27.08 17 4605 13823 90610002
Water intoxication 36.69 27.08 8 4614 583 90623242
Drug interaction 35.53 27.08 56 4566 276397 90347428
Postictal psychosis 35.44 27.08 6 4616 112 90623713
Peritoneal perforation 34.77 27.08 6 4616 126 90623699
Pain 34.45 27.08 5 4617 996336 89627489
Depressed level of consciousness 34.40 27.08 29 4593 72755 90551070
Carcinoid tumour of the stomach 33.25 27.08 6 4616 164 90623661
Brain injury 32.84 27.08 13 4609 7725 90616100
Completed suicide 31.68 27.08 38 4584 145020 90478805
Malignant catatonia 31.29 27.08 6 4616 230 90623595
Electrocardiogram J wave abnormal 30.82 27.08 4 4618 9 90623816
Lip erosion 30.81 27.08 8 4614 1230 90622595
Pyrexia 30.51 27.08 88 4534 660397 89963428
White blood cell count increased 30.15 27.08 26 4596 67215 90556610
Suicidal ideation 30.01 27.08 27 4595 73828 90549997
Cerebral infarction 29.93 27.08 18 4604 26578 90597247
Respiratory depression 29.89 27.08 15 4607 15560 90608265
Cardiogenic shock 28.68 27.08 17 4605 24451 90599374

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
Neuroleptic malignant syndrome 132.36 22.29 58 4465 21414 42595398
Overdose 91.19 22.29 81 4442 105183 42511629
Rhabdomyolysis 90.29 22.29 71 4452 77948 42538864
Toxicity to various agents 81.17 22.29 110 4413 229026 42387786
Altered state of consciousness 78.61 22.29 45 4478 29214 42587598
Hepatic function abnormal 75.36 22.29 54 4469 51513 42565299
Pneumonia aspiration 72.16 22.29 52 4471 50026 42566786
Blood creatine phosphokinase increased 60.22 22.29 46 4477 48292 42568520
Salivary hypersecretion 52.96 22.29 25 4498 10918 42605894
Asphyxia 52.90 22.29 23 4500 8303 42608509
Suicide attempt 51.20 22.29 41 4482 46059 42570753
Water intoxication 49.65 22.29 11 4512 409 42616403
Intentional overdose 41.30 22.29 38 4485 51418 42565394
Parkinsonism 38.69 22.29 20 4503 10603 42606209
Lymphocyte percentage increased 38.48 22.29 8 4515 219 42616593
Delusion 37.78 22.29 22 4501 14712 42602100
White blood cell count increased 37.55 22.29 34 4489 45053 42571759
Stupor 34.93 22.29 13 4510 3140 42613672
Sciatic nerve neuropathy 34.18 22.29 6 4517 64 42616748
Psychiatric symptom 31.19 22.29 13 4510 4228 42612584
Polydipsia 30.48 22.29 13 4510 4475 42612337
Sciatic nerve injury 29.98 22.29 6 4517 135 42616677
Adrenergic syndrome 29.42 22.29 6 4517 149 42616663
Circulatory collapse 26.17 22.29 21 4502 23615 42593197
Neonatal asphyxia 22.72 22.29 6 4517 470 42616342
Hyperthermia 22.65 22.29 15 4508 12559 42604253

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
Neuroleptic malignant syndrome 257.79 20.29 99 8946 33960 110546294
Overdose 219.64 20.29 169 8876 233625 110346629
Altered state of consciousness 216.85 20.29 102 8943 57524 110522730
Toxicity to various agents 176.11 20.29 206 8839 480349 110099905
Intentional overdose 170.44 20.29 116 8929 132385 110447869
Hepatic function abnormal 169.46 20.29 100 8945 89195 110491059
Salivary hypersecretion 140.23 20.29 53 8992 17368 110562886
Pneumonia aspiration 133.55 20.29 83 8962 81150 110499104
Rhabdomyolysis 132.86 20.29 96 8949 120305 110459949
Suicide attempt 124.59 20.29 87 8958 103307 110476947
Blood creatine phosphokinase increased 113.41 20.29 72 8973 73005 110507249
Psychiatric symptom 92.54 20.29 33 9012 9180 110571074
Parkinsonism 82.53 20.29 39 9006 22148 110558106
Delusion 80.00 20.29 39 9006 23716 110556538
White blood cell count increased 69.56 20.29 60 8985 96782 110483472
Water intoxication 69.18 20.29 16 9029 943 110579311
Extrapyramidal disorder 67.25 20.29 37 9008 28830 110551424
Asphyxia 52.90 20.29 25 9020 14190 110566064
Electrocardiogram QT prolonged 48.74 20.29 52 8993 108908 110471346
Cerebral infarction 47.46 20.29 37 9008 51801 110528453
Pyrexia 46.61 20.29 170 8875 898095 109682159
Loss of consciousness 46.36 20.29 68 8977 196238 110384016
Pain 45.79 20.29 11 9034 954944 109625310
Dyspnoea 43.75 20.29 18 9027 1106854 109473400
Depressed level of consciousness 42.32 20.29 49 8996 112229 110468025
Stupor 38.51 20.29 17 9028 8248 110572006
Vasoconstriction 37.12 20.29 10 9035 1100 110579154
Suicidal ideation 37.09 20.29 42 9003 93895 110486359
Polydipsia 36.43 20.29 16 9029 7672 110572582
Somnolence 35.05 20.29 76 8969 297373 110282881
Lymphocyte percentage increased 34.89 20.29 9 9036 837 110579417
Hallucination, auditory 33.60 20.29 23 9022 26374 110553880
Sudden death 32.82 20.29 22 9023 24373 110555881
Schizophrenia 32.57 20.29 21 9024 21805 110558449
Brain oedema 32.44 20.29 24 9021 31074 110549180
Lip erosion 31.98 20.29 10 9035 1856 110578398
Heat illness 30.60 20.29 8 9037 784 110579470
Peritoneal perforation 30.05 20.29 6 9039 175 110580079
Ileus paralytic 29.99 20.29 16 9029 11721 110568533
Glucose tolerance impaired 29.70 20.29 15 9030 9822 110570432
Carcinoid tumour of the stomach 29.69 20.29 6 9039 186 110580068
Renal impairment 29.20 20.29 54 8991 188391 110391863
Hypothermia 29.02 20.29 21 9024 26281 110553973
Blood lactate dehydrogenase increased 28.87 20.29 26 9019 44308 110535946
Cardio-respiratory arrest 28.60 20.29 41 9004 115795 110464459
Fatigue 28.13 20.29 35 9010 1215923 109364331
Lymphocytosis 28.05 20.29 12 9033 5399 110574855
Neutrophil count increased 28.01 20.29 23 9022 34629 110545625
Stevens-Johnson syndrome 27.62 20.29 26 9019 46875 110533379
Adrenergic syndrome 27.50 20.29 6 9039 271 110579983
Postictal psychosis 27.50 20.29 6 9039 271 110579983
Blood pressure decreased 27.34 20.29 40 9005 115051 110465203
Arthralgia 27.19 20.29 15 9030 779617 109800637
Drug hypersensitivity 26.66 20.29 3 9042 454087 110126167
Seizure 26.59 20.29 57 8988 221128 110359126
Aspiration 26.23 20.29 21 9024 30512 110549742
Electrocardiogram J wave abnormal 25.87 20.29 4 9041 24 110580230
Circulatory collapse 25.64 20.29 24 9021 42969 110537285
Restlessness 25.41 20.29 27 9018 56232 110524022
Irritability 25.32 20.29 25 9020 47784 110532470
Brain injury 25.27 20.29 15 9030 13461 110566793
Completed suicide 25.26 20.29 59 8986 242322 110337932
Dystonia 24.88 20.29 19 9026 25786 110554468
Psychotic symptom 24.86 20.29 10 9035 3857 110576397
Abnormal behaviour 23.68 20.29 22 9023 39017 110541237
Withdrawal syndrome 23.65 20.29 20 9025 31360 110548894
Sciatic nerve neuropathy 23.59 20.29 6 9039 527 110579727
Electroencephalogram abnormal 23.41 20.29 11 9034 6162 110574092
Lymphocyte count decreased 23.28 20.29 26 9019 57217 110523037
Persecutory delusion 23.21 20.29 11 9034 6280 110573974
Drug intolerance 23.08 20.29 3 9042 406509 110173745
White blood cell count decreased 22.99 20.29 55 8990 229335 110350919
Hypersensitivity 22.90 20.29 3 9042 403995 110176259
Drug dependence 22.58 20.29 24 9021 49996 110530258
Aggression 22.56 20.29 26 9019 59184 110521070
Neutrophil percentage increased 22.55 20.29 10 9035 4903 110575351
Pain in extremity 22.55 20.29 6 9039 487112 110093142
Akathisia 21.99 20.29 15 9030 17098 110563156
Malignant catatonia 21.92 20.29 6 9039 700 110579554
Muscle rigidity 21.66 20.29 17 9028 24014 110556240
Mania 21.58 20.29 16 9029 20780 110559474
Enterochromaffin cell hyperplasia 21.29 20.29 4 9041 84 110580170
Hyperthermia 21.25 20.29 16 9029 21256 110558998
Drug interaction 21.22 20.29 89 8956 500094 110080160
Sciatic nerve injury 21.20 20.29 6 9039 791 110579463
Liver disorder 21.08 20.29 40 9005 142203 110438051
Platelet count decreased 20.71 20.29 53 8992 230390 110349864
Drug abuse 20.49 20.29 45 9000 177366 110402888

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N05CD03 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Benzodiazepine derivatives
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D011619 Psychotropic Drugs
MeSH PA D014151 Anti-Anxiety Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018682 GABA Agents
MeSH PA D018757 GABA Modulators
CHEBI has role CHEBI:35474 anxiolytic drug
CHEBI has role CHEBI:35717 sedative
CHEBI has role CHEBI:91016 GABA<small><sub>A</sub></small> receptor agonist

Related Drugs by ATC class:

N05CD Benzodiazepine derivatives 14 drugs
brotizolamcinolazepamdoxefazepamestazolamflurazepamloprazolamlormetazepammidazolamnimetazepamnitrazepamquazepamremimazolam 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 1.89 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
Gamma-aminobutyric acid receptor subunit alpha-1 Ion channel ALLOSTERIC MODULATOR Ki 8.28 IUPHAR IUPHAR
Gamma-aminobutyric acid receptor subunit alpha-2 Ion channel ALLOSTERIC MODULATOR Ki 8.28 IUPHAR IUPHAR
Gamma-aminobutyric acid receptor subunit alpha-3 Ion channel ALLOSTERIC MODULATOR Ki 7.80 IUPHAR IUPHAR
Gamma-aminobutyric acid receptor subunit alpha-5 Ion channel ALLOSTERIC MODULATOR Ki 8.26 IUPHAR IUPHAR
GABA-A receptor alpha-1/beta-2/gamma-2 Ion channel Ki 8.70 WOMBAT-PK
GABA-A receptor alpha-2/beta-3/gamma-2 Ion channel Ki 8.70 WOMBAT-PK
GABA-A receptor alpha-3/beta-3/gamma-2 Ion channel Ki 8.35 WOMBAT-PK
GABA-A receptor alpha-5/beta-3/gamma-2 Ion channel Ki 8.84 WOMBAT-PK
GABA-A receptor alpha-1/beta-2/gamma-3 Ion channel Ki 7.46 WOMBAT-PK
GABA-A receptor alpha-1/beta-3/gamma-2 Ion channel Ki 8.47 WOMBAT-PK
GABA A receptor alpha-3/beta-2/gamma-2 Ion channel Ki 8.82 WOMBAT-PK
GABA A receptor alpha-3/beta-2/gamma-3 Ion channel Ki 7.50 WOMBAT-PK
GABA A receptor alpha-5/beta-3/gamma-3 Ion channel Ki 8.42 WOMBAT-PK
GABA A receptor alpha-5/beta-2/gamma-2 Ion channel Ki 9 WOMBAT-PK
GABA A receptor alpha-5/beta-2/gamma-3 Ion channel Ki 8.42 WOMBAT-PK
GABA-A receptor; anion channel Ion channel IC50 8.82 CHEMBL

External reference:

IDSource
N0000166924 NUI
D01230 KEGG_DRUG
C0016296 UMLSCUI
CHEBI:31622 CHEBI
CHEMBL13280 ChEMBL_ID
DB01544 DRUGBANK_ID
D005445 MESH_DESCRIPTOR_UI
3380 PUBCHEM_CID
4193 IUPHAR_LIGAND_ID
2951 INN_ID
620X0222FQ UNII
4460 RXNORM
004091 NDDF
387573007 SNOMEDCT_US
96237009 SNOMEDCT_US

Pharmaceutical products:

None