5-HT6 receptors as emerging targets for drug discovery

5-ht(6) receptors are the latest serotonin receptors to be identified by mo lecular cloning. Their high affinity for a wide range of drugs used in psyc hiatry, coupled with their intriguing distribution in the brain, has stimul ated significant interest. Antisense oligonucleotides, antipeptide antibodi es, selective radioligands, knockout mice, and selective antagonists of the 5-ht(6) receptor have recently become available. Surprisingly, 5-ht(6) rec eptors appear to regulate cholinergic neurotransmission in the brain, rathe r than the expected interaction as modulators of dopaminergic transmission. This interaction predicts a possible role for 5-ht(6) receptor antagonists in the treatment of learning and memory disorders. Furthermore, polymorphi sms in the sequence of the 5-ht(6) receptor gene may provide a genetic tool to further our understanding of the differential responses of patients to antipsychotic medications.