Parkinson’s Disease Psychosis

Treatment of PDP

• Second-generation antipsychotics have an important liability in the treatment of PDP in that they block multiple receptors, such as the dopamine 2 receptor, which may worsen motor symptoms in Parkinson’s disease^11-14
• Other off-target effects of antipsychotics such as blockade of the histamine 1 receptor, alpha receptors, or muscarinic receptors may lead to off-target effects, which may increase the potential for adverse events and side effects^11-13
• In the development of pimavanserin, scientists addressed the off-target effects of previous antipsychotic medications and developed a unique medication that was specifically targeted at the 5HT_2A receptor and eliminated off-target effects of the dopamine 2 receptor, histamine 1 receptor, alpha receptors, and muscarinic receptors^11‑13
• In addition, scientists designed pimavanserin with a unique pharmacologic of inverse agonist activity at the 5HT_2A Inverse agonist activity goes beyond the effect of a normal antagonist; it not only blocks agonists but also reduces the baseline ordinary signaling that occurs in the absence of an agonist¹³
• Finally, unlike antipsychotic medications that were previously used off-label for PDP, such as clozapine or quetiapine, pimavanserin is specifically approved by the US Food and Drug Administration for PDP management

Table 1: Receptor Blockade Profile of Atypical Antipsychotics Versus Pimavanserin^15-17