Professor Vanderbilt University Nasvhille, Tennessee, United States
Introduction:: The serotonin 2B receptor plays a role in a host of cardiopulmonary disease. Specifically, inadvertent agonism of the serotonin 2B receptor in the heart and lungs leads to heart valve disease and pulmonary arterial hypertension. Here, we propose that antagonism of the serotonin 2B receptor can be targeted for cardiopulmoary disease.
Materials and Methods:: We have recently developed novel compounds to target the serotonin 2B receptor for cardiopulmonary disease. Because targeting the 2B receptor in the brain may have negative side effects in humans, we engineered new compounds that are substrates of the P-gp receptor and are thus effluxed from the brain and are systemically restricted.
Results, Conclusions, and Discussions:: To translate these compounds to humans, we have developed systemically restricted compounds that are effective at preventing cardiopulmonary disease in preclinical models. Here, we show the effect of these compounds on models of pulmonary arterial hypertension. Next generation compounds are being developed that can be used for IND-enabling studies and clinical trials in the coming years.