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

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
Intentional overdose 126.09 27.51 69 3484 62435 50539136
Neuroleptic malignant syndrome 102.84 27.51 36 3517 11094 50590477
Altered state of consciousness 101.99 27.51 43 3510 21867 50579704
Overdose 101.06 27.51 71 3482 99656 50501915
Suicide attempt 98.47 27.51 55 3498 51677 50549894
Salivary hypersecretion 79.30 27.51 26 3527 6565 50595006
Extrapyramidal disorder 61.15 27.51 25 3528 11745 50589826
Psychiatric symptom 58.91 27.51 19 3534 4551 50597020
Hepatic function abnormal 57.41 27.51 33 3520 32648 50568923
Parkinsonism 50.11 27.51 20 3533 8827 50592744
Blood creatine phosphokinase increased 47.30 27.51 27 3526 26340 50575231
Loss of consciousness 46.05 27.51 46 3507 104307 50497264
Toxicity to various agents 45.94 27.51 65 3488 212434 50389137
Pneumonia aspiration 45.79 27.51 28 3525 30976 50570595
Electrocardiogram QT prolonged 45.72 27.51 34 3519 51852 50549719
Drowning 42.47 27.51 9 3544 414 50601157
Hypothermia 41.07 27.51 19 3534 11997 50589574
Delusion 33.91 27.51 16 3537 10553 50591018
Peritoneal perforation 33.13 27.51 6 3547 120 50601451
Brain injury 32.00 27.51 13 3540 6001 50595570
Carcinoid tumour of the stomach 31.55 27.51 6 3547 158 50601413
Lip erosion 31.50 27.51 8 3545 816 50600755
White blood cell count increased 31.33 27.51 25 3528 42215 50559356
Stevens-Johnson syndrome 30.47 27.51 19 3534 21733 50579838
Electrocardiogram J wave abnormal 29.55 27.51 4 3549 9 50601562

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 121.53 21.65 53 3720 16095 29554659
Hepatic function abnormal 79.73 21.65 54 3719 39205 29531549
Altered state of consciousness 70.28 21.65 39 3734 19850 29550904
Pneumonia aspiration 66.28 21.65 47 3726 36690 29534064
Rhabdomyolysis 58.82 21.65 54 3719 60754 29510000
Salivary hypersecretion 57.90 21.65 25 3748 7384 29563370
Asphyxia 55.29 21.65 22 3751 5293 29565461
Blood creatine phosphokinase increased 47.07 21.65 40 3733 40604 29530150
Water intoxication 42.62 21.65 10 3763 399 29570355
Lymphocyte percentage increased 37.63 21.65 8 3765 202 29570552
White blood cell count increased 37.56 21.65 34 3739 37482 29533272
Toxicity to various agents 35.35 21.65 72 3701 173589 29397165
Sciatic nerve neuropathy 34.31 21.65 6 3767 51 29570703
Parkinsonism 33.39 21.65 17 3756 7261 29563493
Psychiatric symptom 32.48 21.65 13 3760 3171 29567583
Sciatic nerve injury 31.84 21.65 6 3767 80 29570674
Intentional overdose 31.10 21.65 31 3742 38497 29532257
Stupor 30.78 21.65 12 3761 2732 29568022
Suicide attempt 30.44 21.65 29 3744 34081 29536673
Polydipsia 28.08 21.65 12 3761 3453 29567301
Delusion 26.54 21.65 17 3756 11199 29559555
Overdose 26.42 21.65 41 3732 79778 29490976
Neonatal asphyxia 24.53 21.65 6 3767 286 29570468
Somnolence 22.77 21.65 42 3731 93913 29476841
Persecutory delusion 22.74 21.65 9 3764 2132 29568622

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 218.18 21.77 88 7181 24908 64466555
Altered state of consciousness 153.22 21.77 78 7191 37824 64453639
Salivary hypersecretion 135.18 21.77 51 7218 12062 64479401
Hepatic function abnormal 129.46 21.77 84 7185 64229 64427234
Intentional overdose 110.57 21.77 87 7182 89857 64401606
Pneumonia aspiration 106.16 21.77 72 7197 59199 64432264
Suicide attempt 103.40 21.77 76 7193 70931 64420532
Psychiatric symptom 90.78 21.77 32 7237 6241 64485222
Overdose 86.59 21.77 98 7171 159468 64331995
Blood creatine phosphokinase increased 83.70 21.77 62 7207 58496 64432967
Parkinsonism 80.46 21.77 37 7232 14336 64477127
Rhabdomyolysis 80.30 21.77 73 7196 91653 64399810
White blood cell count increased 70.79 21.77 59 7210 65955 64425508
Delusion 61.11 21.77 33 7236 17981 64473482
Extrapyramidal disorder 58.58 21.77 33 7236 19519 64471944
Water intoxication 52.56 21.77 13 7256 737 64490726
Asphyxia 45.46 21.77 22 7247 9544 64481919
Toxicity to various agents 44.01 21.77 114 7155 363399 64128064
Cerebral infarction 40.52 21.77 35 7234 41009 64450454
Dyspnoea 39.34 21.77 16 7253 718658 63772805
Liver disorder 36.31 21.77 37 7232 53314 64438149
Stupor 35.23 21.77 16 7253 6019 64485444
Lymphocyte percentage increased 35.12 21.77 9 7260 589 64490874
Pain 34.26 21.77 10 7259 553501 63937962
Depressed level of consciousness 34.23 21.77 44 7225 81392 64410071
Pyrexia 33.65 21.77 138 7131 558506 63932957
Lip erosion 32.55 21.77 10 7259 1269 64490194
Electrocardiogram QT prolonged 31.94 21.77 42 7227 79406 64412057
Schizophrenia 31.16 21.77 18 7251 11150 64480313
Sudden death 30.31 21.77 22 7247 20074 64471389
Ileus paralytic 30.17 21.77 16 7253 8399 64483064
Polydipsia 29.52 21.77 14 7255 5807 64485656
Aspiration 28.97 21.77 20 7249 16865 64474598
Hallucination, auditory 28.91 21.77 20 7249 16919 64474544
Peritoneal perforation 28.30 21.77 6 7263 170 64491293
Hypothermia 28.28 21.77 21 7248 19835 64471628
Neutrophil count increased 28.00 21.77 23 7246 25151 64466312
Carcinoid tumour of the stomach 27.71 21.77 6 7263 188 64491275
Electrocardiogram J wave abnormal 27.65 21.77 4 7265 9 64491454
Loss of consciousness 27.31 21.77 55 7214 148310 64343153
Glucose tolerance impaired 25.24 21.77 13 7256 6430 64485033
Somnolence 24.70 21.77 64 7205 203581 64287882
Sciatic nerve neuropathy 24.60 21.77 6 7263 321 64491142
Persecutory delusion 24.19 21.77 11 7258 4147 64487316
Heat illness 23.65 21.77 6 7263 377 64491086
Blood lactate dehydrogenase increased 22.61 21.77 23 7246 33055 64458408
Sciatic nerve injury 22.55 21.77 6 7263 455 64491008
Brain injury 22.46 21.77 14 7255 9951 64481512

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N05CD03 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Benzodiazepine derivatives
MeSH PA D014151 Anti-Anxiety Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D018682 GABA Agents
MeSH PA D018757 GABA Modulators
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D011619 Psychotropic Drugs
MeSH PA D014149 Tranquilizing Agents
CHEBI has role CHEBI:35474 anti-anxiety agents
CHEBI has role CHEBI:35717 hypnotics
CHEBI has role CHEBI:91016 GABAA receptor agonists

Drug Use (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 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