Perospirone (Lullan) is an antagonist of serotonin 5HT2A receptors and dopamine D2 receptors. It also displays affinity towards 5HT1A receptors as a partial agonist.

D2:0.6 nM (Ki), 5-HT2A:1.3 nM (Ki), 5-HT1A:2.9 nM (Ki)

In CHO cells expressing human 5-HT1A receptors, perospirone shows a high affinity (Ki: 0.72 nM) and exhibits partial agonistic efficacy[1]. Perospirone changes epigenetic profiles of neural genes. It can cause DNA methylation changes in cell cultures[2]. Perospirone is an inhibitor of Pgp which interferes directly and indirectly with the function of Pgp. The inhibition of Pgp by perospirone may cause clinically significant drug-drug interactions, especially in the tissue in which it accumulated[3].

Perospirone shows potent 5-HT2 and D2 receptor blocking activities in various animal models in vivo. Perospirone inhibits various dopaminergic behaviours (e.g. methamphetamine-induced hyperactivity and apomorphine-induced stereotypy or climbing behaviour) in rodents. It also inhibits the rat conditioned avoidance response. In behavioural tests, perospirone markedly inhibits serotonergic behaviour (e.g. tryptamine-induced clonic seizures, and p-chlorphenamine-induced hyperthermia) in rats. Perospirone has anxiolytic-like effects and mood stabilizing effects in various animal models. It inhibits motor coordination in a rota-rod test and potentiates the duration of hexobarbital-induced anaesthesia with ED50 values of 34 and 37 mg/kg (p.o.), respectively[1].

Cell lines: Human neuroblastoma SK-N-SH cells. Concentrations: 10.5 or 105.5?nM.Cells are maintained in Eagle's minimal essential medium containing 10% fetal bovine serum for 8 days.The cells are exposed to either a high dose (105.5?nM,assigned as the "high-dose group") or low dose (10.5?nM,assigned as the "low-dose group") of perospirone.The concentrations are determined based on dosages typically used in the clinical setting.The medium is changed on days 2,5,and 8 with media containing perospirone,and on day 9,cells are harvested and processed.

Animal Models: Five-week-old male ICR mice. Formulation: 0.5% methylcellulose solution. Dosages: 10 mg/kg, p.o.