N-(arylpiperazinyl)butylimides of bicyclo [2.2.1]gept-5-en-endo-endo-2, 3-dicarbonic acid – ligands of 5-ht1a and d2 receptors, their neurotropic properties

Abstract

It is known that hetaryl(aryl)piperazines possess important neuropharmacological (anxiolytic, antidepressant, neuroleptic, etc.) properties. In the process of studying the relationship between the structure and properties of N-(arylpiperazinyl) butylimides bicyclo[2.2.1]gept-5-en-endo-endo-2,3-dicarbonic acid (compounds 1-5) the neuropharmacological properties and their affinity for D2 and 5-HT1A receptors have been studied in this work. It has been determined by the radioligands method that arylpiperazines 1-5 possess the high affinity for D2 and 5-HT1A receptors. Compounds 1-5 have been found to have the marked sedative and neuroleptic properties. The compounds (1-5) synthesized revealed a dose-dependent pharmacological effect. In lower doses (5 mg/kg) on the model of the conflict test in rats m-tolyl derivatives had the same anxiolytic effect as buspirone (10 mg/kg); in higher doses (10 mg/kg) all compounds revealed the neuroleptic activity on the model of “Waxy flexibility” catalepsy induction. Compounds of this series in the dose of 10 mg/kg reduced the apomorphine-induced stereotypic behaviour by 33.7-86.5% in rats, as well as a refrence drug haloperidol. All of these compounds are nontoxic, the value of their LD50 ≥ 300 mg/kg.