Bioactive conformation of 1-arylpiperazines at central serotonin receptors

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Abstract
A number of 1-arylpiperazines were characterized as direct-acting serotonin agonists. Conformational parameters of this class that may affect receptor recognition and binding were examined through the analysis of X-ray data and synthesis of rigid analoges. Radioligand binding studies indicate that 2,3,4,4a,5,6-hexahydro-9-(trifluoromethyl)-1H-pyrazino[1,2-a]quinoline, an arylpiperazine that mimics the X-ray conformation of the serotonin agonist 1-(6-chloropyrazin-2-yl)piperazine, exhibits high affinity for serotonin receptors [rat frontal cortex], suggesting that the 2 rings of 1-arylpiperazines are relatively coplanar in the bioactive conformation.