The anxiolytics of new generation, like tandospirone and buspirone, exhibit their therapeutic properties through activation of 5-HT_1A subtype of serotonin receptors.

Many analogs have been synthesized and those that contain the 4-aryl/heteroaryl-piperazinylalkyl group attached to a cyclic imide, have demonstrated an anxiolytic and antidepressive activity.

Recently we obtained new derivatives of the above agents with 4-aryl/heteroaryl-piperazinylalkyl group attached to a complex imide systems which synthesis has already been reported [1].

All the amine derivatives were converted to hydrochlorides and evaluated in vitro for their affinity for 5-HT_1A and 5-HT_2A receptors. The tested compounds showed high affinity for 5-HT_1A (K_i ranged from 10 to 115 nM) and lower affinity for 5-HT_2A (K_i > 181 nM).

Since it is well established that 5-HT_1A ligands possess anxiolytic and antidepressive properties, ten selected compounds were further examined in some behavioural tests in mice.

The investigated new derivatives of selected arrangements azatricycloundecane were administered intraperitoneally (ip) as suspensions in 1% Tween 80 in a constant volume of 0.1 ml/kg. Control groups were given appriopriate amounts of the solvent. Of all the investigated compounds only 1-(2-methoxyphenyl)piperazinylbuthyl derivative of imide I produced antidepressive and antiserotoninergic effects. In the remaining pharmacological tests none of the investigated derivatives did not produce statistically significant effects.

1. J. Kossakowski, B. Kuran, Annals of the Polish Chem. Society, (2003) 284-8

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