Novel Selective Arylpiperazine Ligands for the Serotonin 5-HT1a Receptor

Among the several serotonin membrane receptors, 5-HT(1A)R is one of the most studied. Owing to its widespread presence in CNS and its involvement in a number of diseases, such as anxiety and depression, and cognitive processes, such as learning and memory, 5-HT(1A)R represents a potential target for therapeutically effective drugs. Over the years, our research group has been involved in the design of arylpiperazine compounds as selective 5-HT(1A)R ligands. Here we discuss some recent results in this field and the discovery of 2-[[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]thio]benzoxazole, an antagonist which displays very high affinity (K(i) = 0.094 nM) and selectivity for 5-HT(1A)R. over many other related receptors.