Multi-drug resistance gene (MDR1) and opioid analgesia in horses

Abstract

Opioid absorption in the intestinal tract as well as its effects in the central nervous system is modulated by the P-glycoprotein (P-gp) encoded in the Multi-drug Resistance gene (MDR1) also named ATP-binding cassete, subfamily B, member 1 (ABCB1). This MDR1 gene acts as a selective pump. The expression of this protein in humans and rodents inhibits cellular uptake of substrate opioids. The presence of the intestinal iso-enzyme CYP3A4 associated with MDR1 gene decreases the opioid analgesic activity due to an increase in intestinal metabolism, with a predicted intestinal first pass extraction around 20% which significantly influences the oral availability of opioids. In the central nervous system, P-gp expression decreases opioid neuronal uptake diminishing the analgesic effects. It is unknown if horses have the MDR1 gene and P-gp and what are the effects on opioid absorption, metabolism, and analgesia. Identifying the MDR1 gene and P-gp status in horses is of great importance in order to better understand opioid pharmacologic effects in horses.