Effect of N-Benzylpiperazine, Its Metabolite N-Benzylethylenediamine, and Its Disubstituted Analogue N,N'-Dibenzylpiperazine on the Acquisition, Formation, and Consolidation of Memory in Mice.

Background: N-benzylpiperazine (BZP) belongs to a class of piperazine derivatives (PZDs) that have emerged as recreational drugs. These compounds increase the release of dopamine and serotonin. BZP mimics the psychoactive effects of 3,4-methylenedioxymethylamphetamine. BZP is metabolized to N-benzylethylenediamine (BEDA) and benzylamine. The compound N,N'-dibenzylpiperazine (DBZP) is obtained as a byproduct during the synthesis of BZP. Some PZDs have shown effects on memory; however, there are no previous reports on the activity of BZP, BEDA, and DBZP on memory or on a description of their neuropharmacological profile. We evaluated the effects of these compounds on acquisition, formation, and consolidation memory and explored their neuropharmacological profile in mice.

Methods: We used the passive avoidance test to evaluate the nootropic effect and for memory experiments. We also evaluated the sedative, myo-relaxant, motor coordination, anxiogenic, and locomotor activity of these compounds.

Results: We showed that BZP, its metabolite BEDA, and the disubstituted analogue DBZP enhance the memory and show anxiogenic effects. BZP, as well as DBZP but not BEDA, showed a strong myo-relaxant effect without impairing motor coordination.

Conclusions: BZP and BEDA enhanced the acquisition and consolidation of memory, whereas DBZP only enhances the acquisition of the memory. BEDA and DBZP have an anxiogenic profile similar to that of BZP. BEDA and DBZP represent new psychoactive compounds with the potential to be new BZP-like recreational entities.