Adinazolam

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Adinazolam
Adinazolam.svg
Adinazolam3d.png
Systematic (IUPAC) name
1-(8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,5-a]
[1,4]benzodiazepin-1-yl)-N,N-dimethylmethanamine
Clinical data
Pregnancy cat.
  •  ?
Legal status
  • Schedule IV(US)
Routes Oral
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic
Half-life < 3 hours
Excretion Renal
Identifiers
CAS number 37115-32-5 YesY
ATC code N05BA07
PubChem CID 37632
DrugBank DB00546
ChemSpider 34519 YesY
UNII KN08449444 YesY
KEGG D02770 YesY
ChEBI CHEBI:251412 YesY
ChEMBL CHEMBL328250 YesY
Chemical data
Formula C19H18ClN5 
Mol. mass 351.8
 YesY (what is this?)  (verify)

Adinazolam[1] (marketed under the brand name Deracyn) is a benzodiazepine derivative, and more specifically, a triazolobenzodiazepine (TBZD). It possesses anxiolytic, anticonvulsant, sedative, and antidepressant[2] properties. Adinazolam was developed by Dr. Jackson B. Hester, who was seeking to enhance the antidepressant properties of alprazolam, which he also developed.[3] Adinazolam was never FDA approved and never made available to the public market.

Indications[edit]

Adinazolam is indicated as a treatment for depression and anxiety.

Pharmacodynamics and pharmacokinetics[edit]

Adinazolam binds to peripheral-type benzodiazepine receptors that interact allosterically with GABA receptors as an agonist to produce inhibitory effects.

Metabolism[edit]

Adinazolam was reported to have active metabolites in the August 1984 issue of The Journal of Pharmacy and Pharmacology.[4] The main metabolite is N-desmethyladinazolam.[5] NDMAD has an approximately 25-fold high affinity for benzodiazepine receptors as compared to its precursor, accounting for the benzodiazepine-like effects after oral administration. (REF1) Multiple N-dealkylations lead to the removal dimethyl-aminoethyl side chain, leading to the difference in its potency. (REF5) The other two metabolites are alpha-hydroxyalprazolam and estazolam.[6] In the August 1986 issue of that same journal, Sethy, Francis and Day reported that proadifen inhibited the formation of N-desmethyladinazolam.[7]

Synthesis[edit]

Acylation of the hydrazine derivative with chloroacetyl chloride proceeds on the more basic nitrogen to give the hydrazide. Heating that intermediate in acetic acid closes the triazole ring to give the chloromethylated product. The displacement of chlorine by means of dimethylamine then affords adinazolam.

Adinazolam synthesis:[8]

See also[edit]

References[edit]

  1. ^ FR Patent 2248050
  2. ^ Lahti, Robert A.; Vimala H. Sethy; Craig Barsuhn; Jackson B. Hester (November 1983). "Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine.". Neuropharmacology 22 (11): 1277–82. doi:10.1016/0028-3908(83)90200-9. PMID 6320036. 
  3. ^ "Discovers Award 2004" (PDF). Special Publications. Pharmaceutical Research and Manufacturers of America. April 2004. p. 39. Archived from the original on August 24, 2006. Retrieved August 18, 2006. 
  4. ^ Sethy, Vimala H.; R. J. Collins; E. G. Daniels (August 1984). "Determination of biological activity of adinazolam and its metabolites.". Journal of Pharmacy and Pharmacology 36 (8): 546–8. doi:10.1111/j.2042-7158.1984.tb04449.x. PMID 6148400. 
  5. ^ Peng, G. W. (August 1984). "Assay of adinazolam in plasma by liquid chromatography". Journal of Pharmaceutical Sciences 73 (8): 1173–5. doi:10.1002/jps.2600730840. PMID 6491930. 
  6. ^ Fraser, A. D.; A. F. Isner; W. Bryan (November–December 1993). "Urinary screening for adinazolam and its major metabolites by the Emit d.a.u. and FPIA benzodiazepine assays with confirmation by HPLC". Journal of Analytical Toxicology 17 (7): 427–31. doi:10.1093/jat/17.7.427. PMID 8309217. 
  7. ^ Sethy, Vimala H.; Jonathan W. Francis; J. S. Day (August 1986). "The effect of proadifen on the metabolism of adinazolam". Journal of Pharmacy and Pharmacology 38 (8): 631–2. doi:10.1111/j.2042-7158.1986.tb03099.x. PMID 2876087. 
  8. ^ Hester, J. B.; Rudzik, A. D.; von Voigtlander, P. F. (1980). "1-(Aminoalkyl)-6-aryl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with antianxiety and antidepressant activity". Journal of Medicinal Chemistry 23 (4): 392. doi:10.1021/jm00178a009.  edit