4H-Imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylic
acid, 8-fluoro-5,6-dihydro-5-methyl-6- oxo-, ethyl
ester

CAS  

 78755-81-4

SYNONYMS  

 * Anexate
* Ethyl
8-fluoro-5-methyl-5,6-dihydro-6-oxo-4H-imidazo(1,5-a)(1,4)benzodiazepine
-3-carboxylate
* Flumazenil
* Flumazepil
* Lanexat
* Ro-15-1788

                     *** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : NI2922170
CHEMICAL NAME           : 4H-Imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylic
                          acid, 8-fluoro-5,6-dihydro-5-methyl-6- oxo-, ethyl
                          ester
CAS REGISTRY NUMBER     : 78755-81-4
BEILSTEIN REFERENCE NO. : 4763661
LAST UPDATED            : 199612
DATA ITEMS CITED        : 15
MOLECULAR FORMULA       : C15-H14-F-N3-O3
MOLECULAR WEIGHT        : 303.32
COMPOUND DESCRIPTOR     : Drug
                          Reproductive Effector
                          Human
SYNONYMS/TRADE NAMES :
   * Anexate
   * Ethyl  
   8-fluoro-5-methyl-5,6-dihydro-6-oxo-4H-imidazo(1,5-a)(1,4)benzodiazepine  
   -3-carboxylate
   * Flumazenil
   * Flumazepil
   * Lanexat
   * Ro-15-1788
 
                       *** HEALTH HAZARD DATA ***
 
                        ** ACUTE TOXICITY DATA **
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 5700 ng/kg/C
TOXIC EFFECTS :
   Cardiac - cardiomyopathy including infarction
   Cardiac - arrhythmias (including changes in conduction)
   Cardiac - change in rate
REFERENCE :
   BMJOAE British Medical Journal.  (British Medical Assoc., BMA House,
   Tavistock Sq., London WC1H 9JR, UK)  V.1-    1857- Volume(issue)/page/year:
   304,1415,1992
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - woman
DOSE/DURATION           : 2 mg/kg/2D-I
TOXIC EFFECTS :
   Behavioral - hallucinations, distorted perceptions
   Behavioral - excitement
   Behavioral - aggression
REFERENCE :
   LANCAO Lancet.  (7 Adam St., London WC2N 6AD, UK)  V.1-    1823-
   Volume(issue)/page/year: 339,488,1992
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Human - woman
DOSE/DURATION           : 4 ug/kg
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
   Cardiac - EKG changes not diagnostic of specified effects
   Cardiac - pulse rate increase, without fall in BP
REFERENCE :
   PECAE5 Pediatric Emergency Care.  (Williams & Wilkins, 428 E. Preston St.,
   Baltimore, MD  21202) V.1-    1985-  Volume(issue)/page/year: 11,186,1995
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 4200 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Behavioral - tremor
   Behavioral - rigidity (including catalepsy)
REFERENCE :
   JTCEEM Journal de Toxicologie Clinique et Experimentale.  (SPPIF, B.P.22,
   F-41353 Vineuil, France) V.5-    1985-  Volume(issue)/page/year: 7,223,1987
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 1360 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   DRFUD4 Drugs of the Future.  (J.R. Prous, S.A., Apartado de Correos 540,
   08080 Barcelona, Spain) V.1-    1975/76-  Volume(issue)/page/year:
   7,402,1982
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 85 mg/kg
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
   Behavioral - rigidity (including catalepsy)
REFERENCE :
   JTCEEM Journal de Toxicologie Clinique et Experimentale.  (SPPIF, B.P.22,
   F-41353 Vineuil, France) V.5-    1985-  Volume(issue)/page/year: 7,223,1987
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 1300 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Behavioral - tremor
   Behavioral - rigidity (including catalepsy)
REFERENCE :
   JTCEEM Journal de Toxicologie Clinique et Experimentale.  (SPPIF, B.P.22,
   F-41353 Vineuil, France) V.5-    1985-  Volume(issue)/page/year: 7,223,1987
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 4 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   DRFUD4 Drugs of the Future.  (J.R. Prous, S.A., Apartado de Correos 540,
   08080 Barcelona, Spain) V.1-    1975/76-  Volume(issue)/page/year:
   7,402,1982
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : >1 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   IYKEDH Iyakuhin Kenkyu.  Study of Medical Supplies.  (Nippon Koteisho
   Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan)  V.1- 1970- 
   Volume(issue)/page/year: 23,201,1992
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 143 mg/kg
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
   Behavioral - rigidity (including catalepsy)
REFERENCE :
   JTCEEM Journal de Toxicologie Clinique et Experimentale.  (SPPIF, B.P.22,
   F-41353 Vineuil, France) V.5-    1985-  Volume(issue)/page/year: 7,223,1987
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : >640 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   IYKEDH Iyakuhin Kenkyu.  Study of Medical Supplies.  (Nippon Koteisho
   Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan)  V.1- 1970- 
   Volume(issue)/page/year: 23,201,1992
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : >30 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   IYKEDH Iyakuhin Kenkyu.  Study of Medical Supplies.  (Nippon Koteisho
   Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan)  V.1- 1970- 
   Volume(issue)/page/year: 23,201,1992
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rabbit
DOSE/DURATION           : 2 gm/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Behavioral - tremor
   Behavioral - rigidity (including catalepsy)
REFERENCE :
   JTCEEM Journal de Toxicologie Clinique et Experimentale.  (SPPIF, B.P.22,
   F-41353 Vineuil, France) V.5-    1985-  Volume(issue)/page/year: 7,223,1987
 
                          ** REPRODUCTIVE DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 21 mg/kg
SEX/DURATION            : female 14-20 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Effects on Newborn - behavioral
REFERENCE :
   PNPPD7 Progress in Neuro-Psychopharmacology and Biological Psychiatry.
   (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.6-
      1982-  Volume(issue)/page/year: 17,151,1993
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE                    : 220 mg/kg
SEX/DURATION            : female 11-21 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Effects on Newborn - behavioral
REFERENCE :
   GEPHDP General Pharmacology.  (Pergamon Press Inc., Maxwell House, Fairview
   Park, Elmsford, NY 10523) V.6-    1975-  Volume(issue)/page/year: 22,43,1991
 
                            *** END OF RECORD ***