Behavioral effects and central nervous system levels of the broadly available κ-agonist hallucinogen salvinorin A are affected by P-glycoprotein modulation in vivo.
The Journal of pharmacology and experimental therapeutics June 1, 2012 Eduardo R Butelman, Michael Caspers, Kimberly M Lovell et al. 27 citations
The major efflux transporter P-glycoprotein at the blood-brain barrier modulates the central nervous system effects of the hallucinogen salvinorin A. Pretreatment with either the competing substrate loperamide (0.032-0.32 mg/kg) or the selective blocker tariquidar (0.32-3.2 mg/kg) dose-dependently enhanced salvinorin A-induced ptosis, but not facial relaxation, in nonhuman primates. Neither agent affected the effects of U69,593, a κ-agonist that is a poor P-glycoprotein substrate. Tariquidar (3.2 mg/kg) also increased peak levels of salvinorin A in cerebrospinal fluid after intravenous administration. These findings demonstrate that P-glycoprotein activity can influence salvinorin A's behavioral effects and CNS entry.