Behavioral and qEEG effects of the PDE10A inhibitor THPP-1 in a novel rhesus model of antipsychotic activity

Abstract

SIMA results suggest that PDE10A inhibition produces antipsychotic-like effects in higher species, and that combination therapy with PDE10A inhibitors may produce more robust efficacy compared to monotherapies. EEG and qEEG results confirm that PDE10A inhibition does share some central signaling effects with clinically effective antipsychotics. The present combination therapy results may carry implications for the manner in which clinical testing of PDE10A inhibitors is conducted.

2-Aminopyridines as Potent and Selective Nav1.8 Inhibitors Exhibiting Efficacy in a Nonhuman Primate Pain Model

“…In order to explore the analgesic potential of Na v 1.8 inhibitors such as compound 20 , the protocol was adjusted to allow for presensitization by a 30 min topical capsaicin application to induce hypersensitivity to thermode responses as observed in human pain models . The use of a sensitized assay may align better with the unique Na v 1.8 channel properties of repetitive burst firing and hyperexcitability associated with hyperalgesia observed for patients with chronic pain conditions. , Complete details of the modified rhesus capsaicin sensitized thermode (CST) assay are described in a pending publication …”