Ethyl loflazepate

Ethyl loflazepate

Ethyl loflazepate
Systematic (IUPAC) name
Ethyl 9-Chloro-6-(2-fluorophenyl)-3-oxo-2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraene-4-carboxylate
Clinical data
AHFS/Drugs.com
Pregnancy cat.
  • ?
Legal status
Routes Oral
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic
Half-life ?
Excretion Renal
Identifiers
CAS number  N
ATC code N05
PubChem
DrugBank
ChemSpider  YesY
UNII  N
KEGG  N
ChEMBL  YesY
Chemical data
Formula C18H14ClFN2O3 
Mol. mass 360.7
 N   

Ethyl loflazepate[1] (marketed under the brand names Meilax, Ronlax and Victan)[2][3][4] is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.[5] In animal studies it was found to have low toxicity, although in rats evidence of pulmonary phospholipidosis occurred with pulmonary foam cells developing with long-term use of very high doses.[6] Its elimination half-life is 51 hours - 103 hours.[7] Its mechanism of action is similar to other benzodiazepines. Ethyl loflazepate also produces an active metabolite which is stronger than the parent compound.[8] Ethyl loflazepate was designed to be a prodrug for descarboxyloflazepate, its active metabolite. It is the active metabolite which is responsible for most of the pharmacological effects rather than ethyl loflazepate.[9] The main metabolites of ethyl loflazepate are descarbethoxyloflazepate, loflazepate and 3-hydroxydescarbethoxyloflazepate.[10] Accumulation of the active metabolites of ethyl loflazepate are not affected by those with renal failure or impairment.[11] The symptoms of an overdose of ethyl loflazepate include sleepiness, agitation and ataxia. Hypotonia may also occur in severe cases. These symptoms occur much more frequently and severely in children.[12] Death from therapeutic maintenance doses of ethyl loflazepate taken for 2 – 3 weeks has been reported in 3 elderly patients. The cause of death was asphyxia due to benzodiazepine toxicity.[13] High doses of the antidepressant fluvoxamine may potentiate the adverse effects of ethyl loflazepate.[14]

Ethyl loflazeplate is commercialized in Mexico, but not prescribed very often, under the trade name Victan. It is officially approved for the following conditions:[15][16]

See also

References

  1. ^ DE Patent 2012190
  2. ^ Ba, BB; Iliadis, A; Durand, A; Berger, Y; Cano, JP (Oct 1988). "New approach in bioavailability study of two formulations of ethyl loflazepate". Arzneimittel-Forschung 38 (10): 1486–9.  
  3. ^ Ba, BB; Iliadis, A; Cano, JP (1989). "Pharmacokinetic modeling of ethyl loflazepate (Victan) and its main active metabolites". Annals of biomedical engineering 17 (6): 633–46.  
  4. ^ "Benzodiazepine Names". non-benzodiazepines.org.uk. Retrieved 2009-04-05. 
  5. ^ Ueki, S; Watanabe, S; Yamamoto, T; Shibata, S; Shibata, K; Ohta, H; Ikeda, K; Kiyota, Y; Sato, Y (Nov 1983). "Behavioral effects of ethyl loflazepate and its metabolites". Nippon yakurigaku zasshi. Folia pharmacologica Japonica 82 (5): 395–409.  
  6. ^ Mazue, G; Berthe, J; Newmann, AJ; Brunaud, M (Oct 1981). "A toxicologic evaluation of ethyl fluclozepate (CM 6912)". International journal of clinical pharmacology, therapy, and toxicology 19 (10): 453–72.  
  7. ^ Cautreels, W; Jeanniot, JP (Nov 1980). "Quantitative analysis of CM 6912 (ethyl loflazepate) and its metabolites in plasma and urine by chemical ionization gas chromatography mass spectrometry. Application to pharmacokinetic studies in man". Biomedical mass spectrometry 7 (11–12): 565–71.  
  8. ^ Sakai, Y; Namima, M (Apr 1985). "Inhibitory effect on 3H-diazepam binding and potentiating action on GABA of ethyl loflazepate, a new minor tranquilizer". Japanese journal of pharmacology 37 (4): 373–9.  
  9. ^ Chambon, JP; Perio, A; Demarne, H; Hallot, A; Dantzer, R; Roncucci, R; Bizière, K (1985). "Ethyl loflazepate: a prodrug from the benzodiazepine series designed to dissociate anxiolytic and sedative activities". Arzneimittel-Forschung 35 (10): 1573–7.  
  10. ^ Davi, H; Guyonnet, J; Sales, Y; Cautreels, W (1985). "Metabolism of ethyl loflazepate in the rat, the dog, the baboon and in man". Arzneimittel-Forschung 35 (7): 1061–5.  
  11. ^ Ba, BB; Iliadis, A; Durand, A; Berger, Y; Necciari, J; Cano, JP (1989). "Effect of renal failure on the pharmacokinetics of ethyl loflazepate (Victan) in man". Fundamental & clinical pharmacology 3 (1): 11–7.  
  12. ^ Pulce C, Mollon P, Pham E, Frantz P, Descotes J (April 1992). "Acute poisonings with ethyle loflazepate, flunitrazepam, prazepam and triazolam in children". Vet Hum Toxicol 34 (2): 141–3.  
  13. ^ Kamijo, Y; Hayashi, I; Nishikawa, T; Yoshimura, K; Soma, K (Mar 2005). "Pharmacokinetics of the active metabolites of ethyl loflazepate in elderly patients who died of asphyxia associated with benzodiazepine-related toxicity". Journal of analytical toxicology 29 (2): 140–4.  
  14. ^ Imanishi, T; Onozawa, K; Hayashi, A; Baba, J (Dec 2001). "Effects of fluvoxamine on both the desired anxiolytic effect and the adverse motor incoordination and amnesia induced by benzodiazepines". Nippon yakurigaku zasshi. Folia pharmacologica Japonica 118 (6): 403–10.  
  15. ^ "Victan". saludzac.gob.mx/. Retrieved 2009-12-25. 
  16. ^ "VICTAN". Farmacia Guerra. Retrieved 2009-12-25. 

External links

  • (Japanese) Meilax Fine Granules