PillarMaxQ (P6AS) functions as an in vivo sequestration agent for methamphetamine and fentanyl. We use 1H NMR and isothermal titration calorimetry to glean information on the geometry and strength of the P6AS•drug complexes. P6AS forms tight complexes with fentanyl (Kd = 9.8 nM), PCP (17.1 nM), MDMA (25.5 nM), mephedrone (52.4 nM), and methamphetamine (101 nM). P6AS has good in vitro biocompatibility according to MTS metabolic, Adenylate Kinase cell death, and hERG ion channel inhibition assays, and the Ames fluctuation test. The no observed adverse effect level derived from a maximum tolerated dose study for P6AS was 45 mg kg-1. The hyperlocomotion of mice treated with methamphetamine (0.5 mg kg-1) can be ameliorated by subsequent treatment with P6AS (35.7 mg kg-1) 5-minutes later, whereas the hyperlocomotion of mice treated with fentanyl (0.1 mg kg-1) can be controlled by treatment with P6AS (5 mg kg-1) up to 15-minutes later. P6AS has significant potential for development as a broad spectrum in vivo sequestration agent.
Details of the 1H NMR and ITC studies, in vitro and in vivo toxicology assays, and in vivo efficacy studies.