2007 issue 2


Volume 23, issue 2

Review article

Tofisopam. The investigation of the mechanism of 2,3-benzodiazepines (homoftalazines) action

Adam Hamed1, Anna Skórzewska2, Małgorzata Lehner2, Adam Płaźnik1,2
1. Zakład Farmakologii Klinicznej i Doświadczalnej Akademii Medycznej w Warszawie
2. Zakład Neurochemii Instytutu Psychiatrii i Neurologii w Warszawie
Farmakoterapia w Psychiatrii i Neurologii, 2007, 2, 109–117
Keywords: anxiolytic drugs, basal ganglia, 2.3-benzodiazepines, homoftalazines, tofi sopam, preclinical studies


A great number of anxiolytics used in the clinical practice is structurally related to 1,4-benzodiazepines. Tofi sopam is the first derivative which differs from the so-called classical benzodiazepines in the position of the nitrogen atoms i.e. in the case of tofi sopam they are vicinals (2,3-).The difference in its structure is suspected to be responsible for the different pharmacological and clinical profile of tofisopam.
Since 60’, several members of the 2,3-benzodiazepine (homophtalazines) family have been synthesized. Some of this compounds- tofizopam (Grandaxin®), girizopam, narizopam – exert anxiolytic and antipsychotic activites. Sites in the brain where actions homophtalazines are mediated differ from those of 1,4-benzodiazepines.
Chemical lesioning of the striato-pallido-nigral system, surgical transactions of the striato-nigral pathway and activation of c-fos expression in basal ganglia after application of 2,3-benzodiazepines suggest that these compounds mainly bind to projecting neurons in the striatum. The mechanism of homophtalazines action is still unknown. Tofizopam increases the affi nity of benzodiazepine receptors (a benzodiazepine binding site on GABA-A receptors) for 1,4-benzodiazepines. The psychoactive effect of tofizopam seems to be mediated by influencing GABAergic transmission, however, in contrast to 1,4-benzodiazepines, tofizopam has no anticonvulsive potency. Tofiopam also exert an inhibitory infl uence on the dopaminergic system. Few studies on the mechanism of action of 2,3-benzodiazepines indicate their possible role in opioid signal transduction. The present paper summarizes the main pharmacological actions of the 2,3-benzodiazepines family.

Address for correspondence:
Zakład Neurochemii
Instytut Psychiatrii i Neurologii.
ul. Sobieskiego 9, 02-957 Warszawa