Behavioural and radioligand analysis of the effect of two new piperazine derivatives with anxiolytic properties.
The experiments were carried out on Wistar rats, using a conflict situation consisting in opposition of two motivations: positive (water drinking) and negative (electrical pain). Two newly-synthesized piperazine derivatives with proved psychotropic activity (4P-183 and GP4) were studied and compared with the classical benzodiazepine tranquilizing agent diazepam. Parallel with this, the affinity of these compounds to the benzodiazepine receptor in mouse brain was tested (radioligand binding of 3H-diazepam), as well as the changes in the characteristics of binding (dissociation constant and density of the receptors) after 14-day administration o doses equal to 1/3 LD50 of the two compounds. The results indicate the existence of anxiolytic (anticonflict) activity in both compounds. The fact that the above-mentioned derivatives do not interact with 3H-diazepam (in vitro), changing above all the dissociation constant after chronic administration, suggests predominantly nonspecific type of binding to the receptors. It is possible that their anxiolytic activity is associated with indirect interactions with one of the components of the GABA-benzodiazepine receptor complex, similar to the atypical tranquillizers.
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry; D003220:Conflict, Psychological; D003975:Diazepam / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000032:analysis
D000578:Amidines; D014151:Anti-Anxiety Agents; D006146:Guanidines; D010879:Piperazines; D011963:Receptors, GABA-A; C050210:1-benzyl-4-(guanidinoiminomethyl)piperazine; C058604:GP 4; D003975:Diazepam