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

Stem definition	Drug id	CAS RN
diazepam derivatives	1202	1622-62-4

Description:

Molecule

Description

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:

Dose	Unit	Route
1	mg	O
1	mg	P

ADMET properties:

Property	Value	Reference
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

Approvals:

Date	Agency	Company	Orphan
Jan. 1, 1976	YEAR INTRODUCED

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Intentional overdose	148.28	25.71	86	4759	67119	53277102
Suicide attempt	140.54	25.71	79	4766	58089	53286132
Neuroleptic malignant syndrome	131.10	25.71	47	4798	11986	53332235
Altered state of consciousness	129.66	25.71	57	4788	24779	53319442
Overdose	129.20	25.71	94	4751	107642	53236579
Psychiatric symptom	80	25.71	26	4819	4927	53339294
Hepatic function abnormal	72.82	25.71	44	4801	36855	53307366
Salivary hypersecretion	64.03	25.71	24	4821	6919	53337302
Extrapyramidal disorder	63.17	25.71	28	4817	12374	53331847
Blood creatine phosphokinase increased	60.91	25.71	36	4809	28949	53315272
Pneumonia aspiration	57.80	25.71	37	4808	34264	53309957
Parkinsonism	54.59	25.71	23	4822	8990	53335231
Stevens-Johnson syndrome	52.88	25.71	31	4814	24551	53319670
Toxicity to various agents	52.86	25.71	81	4764	219517	53124704
Delusion	51.34	25.71	24	4821	11985	53332236
Depressed level of consciousness	48.71	25.71	40	4805	54388	53289833
Carcinoid tumour of the stomach	48.50	25.71	9	4836	158	53344063
Hypothermia	46.43	25.71	23	4822	13033	53331188
Hypergastrinaemia	45.29	25.71	8	4837	105	53344116
Rhabdomyolysis	42.94	25.71	34	4811	43889	53300332
Loss of consciousness	42.38	25.71	52	4793	114160	53230061
Enterochromaffin cell hyperplasia	42.24	25.71	7	4838	61	53344160
White blood cell count increased	41.40	25.71	34	4811	46211	53298010
Electrocardiogram QT prolonged	41.39	25.71	37	4808	56366	53287855
Drowning	39.70	25.71	9	4836	436	53343785
Lip erosion	37.76	25.71	10	4835	927	53343294
Respiratory depression	35.27	25.71	19	4826	12787	53331434
Water intoxication	33.75	25.71	8	4837	472	53343749
Peritoneal perforation	31.40	25.71	6	4839	124	53344097
Neuroendocrine tumour	31.06	25.71	8	4837	665	53343556
Pain	30.46	25.71	8	4837	588390	52755831
Pyrexia	29.70	25.71	92	4753	403101	52941120
Liver disorder	28.77	25.71	26	4819	40129	53304092
Electrocardiogram J wave abnormal	28.52	25.71	4	4841	9	53344212
Brain injury	27.99	25.71	13	4832	6392	53337829
Aspiration	27.70	25.71	15	4830	10195	53334026
Sudden death	27.65	25.71	15	4830	10233	53333988

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Neuroleptic malignant syndrome	204.33	19.86	84	5171	17411	32490860
Rhabdomyolysis	91.00	19.86	80	5175	67185	32441086
Water intoxication	90.23	19.86	20	5235	483	32507788
Hepatic function abnormal	89.60	19.86	67	5188	44773	32463498
Pneumonia aspiration	78.89	19.86	60	5195	41096	32467175
Altered state of consciousness	72.94	19.86	45	5210	21952	32486319
Salivary hypersecretion	59.18	19.86	28	5227	8060	32500211
Asphyxia	58.93	19.86	25	5230	5575	32502696
Psychiatric symptom	54.96	19.86	21	5234	3573	32504698
Blood creatine phosphokinase increased	53.39	19.86	50	5205	45426	32462845
Polydipsia	50.23	19.86	20	5235	3797	32504474
Suicide attempt	46.72	19.86	43	5212	38201	32470070
White blood cell count increased	41.96	19.86	42	5213	41360	32466911
Overdose	39.83	19.86	59	5196	87018	32421253
Toxicity to various agents	39.48	19.86	88	5167	177953	32330318
Delusion	38.87	19.86	25	5230	13083	32495188
Lymphocyte percentage increased	35.09	19.86	8	5247	220	32508051
Parkinsonism	33.68	19.86	19	5236	7850	32500421
Stupor	33.54	19.86	14	5241	2995	32505276
Intentional overdose	31.21	19.86	36	5219	41565	32466706
Sciatic nerve neuropathy	30.64	19.86	6	5249	77	32508194
Sciatic nerve injury	29.29	19.86	6	5249	98	32508173
Liver disorder	28.24	19.86	30	5225	31624	32476647
Persecutory delusion	26.47	19.86	11	5244	2328	32505943
Hallucination, auditory	26.46	19.86	18	5237	10332	32497939
Insomnia	26.11	19.86	53	5202	100295	32407976
Somnolence	26.04	19.86	54	5201	103743	32404528
Mania	25.22	19.86	17	5238	9615	32498656
Schizophrenia	24.67	19.86	17	5238	9967	32498304
Sudden death	23.28	19.86	20	5235	16212	32492059
Seizure	22.57	19.86	51	5204	103803	32404468
Neonatal asphyxia	22.38	19.86	6	5249	325	32507946
Depressed level of consciousness	22.07	19.86	30	5225	40817	32467454
Delirium	21.78	19.86	31	5224	44015	32464256
Dyspnoea	20.67	19.86	17	5238	362028	32146243
Eosinophil count increased	20.11	19.86	14	5241	8341	32499930

Pharmacologic Action:

Source	Code	Description
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	minor tranquilisers
CHEBI has role	CHEBI:35717	sedatives
CHEBI has role	CHEBI:91016	GABAA receptor agonists

Drug Use (View source of the data)

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	1.89	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Gamma-aminobutyric acid receptor subunit alpha-1	Ion channel	P14867	GBRA1_HUMAN	ALLOSTERIC MODULATOR	Ki	8.28		IUPHAR	IUPHAR
Gamma-aminobutyric acid receptor subunit alpha-2	Ion channel	P47869	GBRA2_HUMAN	ALLOSTERIC MODULATOR	Ki	8.28		IUPHAR	IUPHAR
Gamma-aminobutyric acid receptor subunit alpha-3	Ion channel	P34903	GBRA3_HUMAN	ALLOSTERIC MODULATOR	Ki	7.80		IUPHAR	IUPHAR
Gamma-aminobutyric acid receptor subunit alpha-5	Ion channel	P31644	GBRA5_HUMAN	ALLOSTERIC MODULATOR	Ki	8.26		IUPHAR	IUPHAR
GABA-A receptor alpha-1/beta-2/gamma-2	Ion channel	P14867 P18507 P47870	GBRA1_HUMAN GBRG2_HUMAN GBRB2_HUMAN		Ki	8.70		WOMBAT-PK
GABA-A receptor alpha-2/beta-3/gamma-2	Ion channel	P18507 P28472 P47869	GBRG2_HUMAN GBRB3_HUMAN GBRA2_HUMAN		Ki	8.70		WOMBAT-PK
GABA-A receptor alpha-3/beta-3/gamma-2	Ion channel	P18507 P28472 P34903	GBRG2_HUMAN GBRB3_HUMAN GBRA3_HUMAN		Ki	8.35		WOMBAT-PK
GABA-A receptor alpha-5/beta-3/gamma-2	Ion channel	P18507 P28472 P31644	GBRG2_HUMAN GBRB3_HUMAN GBRA5_HUMAN		Ki	8.84		WOMBAT-PK
GABA-A receptor alpha-1/beta-2/gamma-3	Ion channel	P14867 P47870 Q99928	GBRA1_HUMAN GBRB2_HUMAN GBRG3_HUMAN		Ki	7.46		WOMBAT-PK
GABA-A receptor alpha-1/beta-3/gamma-2	Ion channel	P14867 P18507 P28472	GBRA1_HUMAN GBRG2_HUMAN GBRB3_HUMAN		Ki	8.47		WOMBAT-PK
GABA A receptor alpha-3/beta-2/gamma-2	Ion channel	P18507 P34903 P47870	GBRG2_HUMAN GBRA3_HUMAN GBRB2_HUMAN		Ki	8.82		WOMBAT-PK
GABA A receptor alpha-3/beta-2/gamma-3	Ion channel	P34903 P47870 Q99928	GBRA3_HUMAN GBRB2_HUMAN GBRG3_HUMAN		Ki	7.50		WOMBAT-PK
GABA A receptor alpha-5/beta-3/gamma-3	Ion channel	P28472 P31644 Q99928	GBRB3_HUMAN GBRA5_HUMAN GBRG3_HUMAN		Ki	8.42		WOMBAT-PK
GABA A receptor alpha-5/beta-2/gamma-2	Ion channel	P18507 P31644 P47870	GBRG2_HUMAN GBRA5_HUMAN GBRB2_HUMAN		Ki	9		WOMBAT-PK
GABA A receptor alpha-5/beta-2/gamma-3	Ion channel	P31644 P47870 Q99928	GBRA5_HUMAN GBRB2_HUMAN GBRG3_HUMAN		Ki	8.42		WOMBAT-PK
GABA-A receptor; anion channel	Ion channel		GBRP_RAT GBRB1_RAT GBRD_RAT GBRG2_RAT GBRA5_RAT GBRA3_RAT GBRG1_RAT GBRA2_RAT GBRA4_RAT GBRG3_RAT GBRA6_RAT GBRA1_RAT GBRB3_RAT GBRB2_RAT Q91ZM7_RAT GBRE_RAT		IC50	8.82		CHEMBL

External reference:

ID	Source
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