IN VITRO SCREENS
Initial evaluation of assets includes assessment of functional activity against a broad panel of human recombinant targets in vitro. The primary goal is to rule out interactions with the opioid receptors or with other biological targets that may lead to abuse or dependence. In addition, the panels allow for identification of undesirable off-target activity profiles that could negatively impact or halt the development of candidate drugs.
Functional activity scan
Functional activity is assessed in 78 assays against GPCR, enzyme, ion channel, neurotransmitter transporters, and nuclear hormone receptors at 10 concentrations across four log orders.
Functional activity at µ-, κ-, and δ-opioid receptors is assessed in agonist and antagonist mode in the functional activity scan. Activity at these receptors is also assessed in positive allosteric modulator (PAM) mode at 10 concentrations across four log orders.
GABAA (gamma-Aminobutyric acid) receptor
Functional activity (blocker/opener) at the GABAA receptor is assessed in the functional activity scan. Activity at the GABAA α1/β2/γ2 receptor subunits is also assessed in PAM mode at 3-6 concentrations across 3-4 log orders.
This work was conducted by PsychoGenics Inc. (Paramus, NJ) in collaboration with PSPP, NINDS, NIH under contract # 75N95019D00026