New discoveries in the development of antipsychotics with novel mechanisms of action: beyond the atypical antipsychotics with serotonin dopamine antagonism

Abstract

Antipsychotic innovation can be divided into three eras. The first era began with the serendipitous discovery of the classical antipsychotic neuroleptics, later found to mediate their therapeutic actions by blocking D2 dopamine receptors, particularly in the mesolimbic dopamine pathway [1]. From the late 1950s through the 1980s, a large number of effective compounds sharing this mechanism of action were thus discovered and marketed. The use of such classical antipsychotic compounds has now given way to the era of “atypical antipsychotics” which began in the late 1980s when the atypical properties of clozapine were observed, and attributed at least in part to the simultaneous blockade of serotonin 2A receptors as well as D2 dopamine receptors [1–3]. We are currently nearing the end of this era now that several SDAs (serotonin dopamine antagonists) have been discovered and marketed, with a few more in the late stages of clinical development. These compounds have been discussed and emphasised in many of the preceding chapters of this book.