NU-1223, a simplified analog of alstonine, with 5-HTR agonist-like activity, rescues memory deficit and positive and negative symptoms in subchronic phencyclidine mouse model of schizophrenia.

The serotonin (5-HT) receptor(R) is a widely distributed G-protein-coupled receptor, expressed abundantly in the central nervous system. Alstonine is a natural product that has significant properties of atypical antipsychotic drugs (AAPDs), in part attributed to 5-HTR agonism. Based on alstonine, we developed NU-1223, a simplified β carboline analog of alstonine, which shows efficacies comparable to alstonine and to other 5-HTR agonists, Ro-60-0175 and lorcaserin.