Valium Research Today is a free monthly online journal that collates and summarizes the latest research about Valium, including details on diazepam, depression, side-effects, withdrawal.

Novel 3-iodo-8-ethoxypyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide as promising lead for design of alpha5-inverse agonist useful tools for therapy of mnemonic damage.

Guerrini G, Ciciani G, Cambi G, Bruni F, Selleri S, Besnard F, Montali M, Martini C, Ghelardini C, Galeotti N, Costanzo A

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Firenze, Via U. Schiff, 6, 50019 Polo Scientifico, Sesto Fiorentino (Firenze), Italy. gabriella.guerrini@unifi.it

The synthesis and the binding study of new 3-iodiopyrazolo[5,1-c][1,2,4] benzotriazine 5-oxides 8-alkyloxy substituted are reported. The replacement at position 3 with an iodine atom, with respect to substituents capable to form a three centered hydrogen bond and/or to form pi-pi stacking interaction with receptor protein, gave high affinity ligands, independently of the 8-alkyloxy substituent. High-affinity ligands were studied in mice in vivo for their pharmacological effects, considering five potential benzodiazepine actions: anxiolytic-like effects, motor coordination, anticonvulsant action, mouse learning and memory impairment, and ethanol-potentiating action. Compounds 5c and 5'c have an inverse agonist profile and for the first time is evidenced a pro-mnemonic activity. These compounds were evaluated also for their binding at Benzodiazepine site on GABA(A) receptor complex (GABA(A)/BzR complex) subtype to evaluate their subtype selectivity.

Published 13 March 2007 in Bioorg Med Chem, 15(7): 2573-86.
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