Halazepam

Halazepam

Halazepam
Systematic (IUPAC) name
7-chloro- 5-phenyl- 1-(2,2,2-trifluoroethyl) -1,3-dihydro- 2H-1,4-benzodiazepin- 2-one
Clinical data
AHFS/Drugs.com
MedlinePlus
Pregnancy cat.
  • ?
Legal status
Routes Oral
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic
Half-life 14 hours (drug), 50-100 hours (metabolites).
Excretion Renal
Identifiers
CAS number  YesY
ATC code N05
PubChem
DrugBank
ChemSpider  YesY
UNII  YesY
KEGG  YesY
ChEMBL  YesY
Synonyms 9-chloro- 6-phenyl- 2-(2,2,2-trifluoroethyl)- 2,5-diazabicyclo[5.4.0] undeca- 5,8,10,12-tetraen -3-one
Chemical data
Formula C17H12ClF3N2O 
Mol. mass 352.7
 YesY   

Halazepam[1] is a benzodiazepine derivative and is marketed under the brand names Alapryl and Pacinone It is no longer marketed in the United States. It had been marketed under the name Paxipam, but was withdrawn by its manufacturer, Schering Plough, for poor sales. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It is a trifluoroethyl derivative of nordazepam.[2] While its structure may be similar to chlordiazepoxide and diazepam, it has both less toxicity and less tendency to cause paradoxical hostility and aggression than either of them.[3] Halazepam has active benzodiazepine metabolites.[4]

Contents

  • Medical uses 1
  • Adverse effects 2
  • Interactions 3
  • Clinical Data 4
  • Pharmacokinetics and pharmacodynamics 5
  • Regulatory Information 6
    • Code of Federal Regulations Title 6.1
    • Code of Federal Regulations Section 6.2
  • Other names 7
  • See also 8
  • References 9
  • External links 10

Medical uses

Halazepam is indicated for the treatment of anxiety.[5]

Adverse effects

Adverse effects include drowsiness, confusion, dizziness, and sedation.[6] Gastrointestinal side effects have also been reported including dry mouth and nausea.[7]

Interactions

The central nervous system effects of benzodiazepines may be affected by the acute ethanol ingestion. Since CYP-450 hepatic enzymes are inhibited, the mechanism could be decreased clearance of the benzodiazepines. In addition, it has been reported that benzodiazepines can induce the cognitive deficits significantly in patients who drink large amounts of alcohol.[8]

Clinical Data

Fann et al. confirmed that halazepam had anti-anxiety properties of (Hamilton Anxiety Scale, Symptom Check list) by administering halaxepam to 46 anxious neurotics at 2 different dose levels, 80 and 160 mg/day vs placebo. In this study, halazepam is safe and efficient enough because it had only mild drowsiness side effect. In addition, the main source of benzodiazepine abuse, Euphoriant effects, were not present. Clinical indications are apparently those of other sort of benzodiazepines as a nontoxic, efficacious compound for treatment of anxiety.[9]

Pharmacokinetics and pharmacodynamics

[10]

Onset of action Intermediate to slow
Plasma half life 14 hr for parent drug and 30-100 hr for its metabolite
Peak plasma levels 1-3 hr for parent drug and 3-6 hf for its metabolite
Metabolism Metabolized into desmethyldiazepam and 3-hydroxyhalazepam (in the liver)
Excretion Excreted through kidneys
Protein binding 98% bound to plasma protein

Regulatory Information

Regulation by Unites States

Halazepam is classified as a schedule 4 with a corresponding code 2762 by Drug Enforcement Administration (DEA). [11]

Code of Federal Regulations Title

21 CFR Part 1308

Code of Federal Regulations Section

21 CFR 1308.14


Other names

Halazepam (English, French, German, Spanish)

Alazepam (Italian)

Halazepam (Danish, Dutch, Swedish)

Halatsepaami (Finnish)

Halazepame (Portuguese)

See also

References

  1. ^ FR Patent 1518382
  2. ^ Greenblatt, D. J.; A. Locniskar and R. I. Shader (June 12, 1982). "Halazepam, another precursor of desmethyldiazepam". Lancet 1 (8285): 1358–9.  
  3. ^ Fann, W. E.; W. M. Pitts and J. C. Wheless (Mar–Apr 1982). "Pharmacology, efficacy, and adverse effects of halazepam, a new benzodiazepine". Pharmacotherapy 2 (2): 72–9.  
  4. ^ Jochemsen R, Breimer DD (1984). "Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles". Curr Med Res Opin. 8. Suppl 4: 60–79.  
  5. ^ Lozano, Lozano, Lozano, et al. (1990). "[Open clinical study of the efficacy and safety of Halazepam in anxiety disorders]". Actas Luso Esp Neurol Psiquiatr Cienc Afines (in Spanish; Castilian) 18 (4): 205–11.  
  6. ^ MA, Gagnon (1977). "Effects of halazepam and diazepam on the motor coordination of geriatric subjects". Eur J Clin Pharmacol 11: 443-8. 
  7. ^ GC, Aden (1980). "Effectiveness of bedtime dosing of benzodiazepines: a placebo- controlled comparison of halazepam and clorazepate". Clin Ther 3: 209-18. 
  8. ^ Nichols, JM (1993). "A comparison of the effect of lorazepam on memory in heavy and low social drinkers". Psychopharmacology (Berl): 475-82. 
  9. ^ Fann, William E (1982). "Halazepam in the treatment of recurrent anxiety attacks in chronically anxious outpatients: A double-blind placebo controlled study". Current Therapeutic Research 32: 906-910. 
  10. ^ Quitkin, Frederick M. ... (1998). Current therapeutic drugs (2nd ed. ed.). Washington: American Psychiatric Press. p. 166.  
  11. ^ "Dextromethorphan". U.S. Food and Drug Administration. U.S. Food and Drug Administration. Retrieved 22 November 2014. 

External links

  • Inchem - Halazepam