Novel serotonin receptor ligands for medical use

It is well known that serotonin receptor ligands can be useful drugs for treatment of diseases outside the central nervous system (CNS). The main target organs for non-CNS indications are the gastrointestinal system, bladder and cardiovascular system. Sev eral serotonin receptor ligands are in development for treatment of diseases related to these organs and BMI is currently performing a clinical phase II study aiming to document beneficial effects of 5-HT4 (a serotonin receptor) antagonists in heart failu re (CHF). The current application relates to a new project where we aim to develop serotonin receptor ligands with tissue-specific distribution, by chemically modifying known receptor ligands without interfering with their biological activity. This acti vity is not limited to 5-HT4 receptor ligands, but will also include ligands of other 5-HT receptors. In principle, our new concept applies to all serotonin receptors located outside the CNS, and we have therefore provided chemical examples to illustrate the concept for several different serotonin receptors. Our initial focus will, however, be on those receptors for which the biological effects are best known, and where a medical need is most obvious.