Adinazolam

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 arealpha-hydroxyalprazolam and estazolam.^[6] In the August 1986 issue of that same journal, Sethy, Francis and Day reported thatproadifen 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.