Opiate Peptides And The Blood-Brain Barrier

Opioid peptides play a significant role in the treatment of pain. Despite this promise, few opioid peptides have shown true clinical viability for the alleviation of centrally mediated pain. The leading factor for the observed inactivity of these peptides is the blood-brain barrier (BBB). The BBB acts as a metabolic and transport barrier, preventing the delivery of substances to the central nervous system (CNS). The innate physical makeup of the BBB (tight junctions and limited pinocytotic activity) directly limits the transport of peptides, which are generally hydrophilic in nature, into the brain. In addition, the BBB forms a highly active metabolic barrier that rapidly degrades peptides. Finally, the BBB expresses a number of efflux systems that actively remove peptides from the CNS. Through the alteration of the biochemical and structural composition of opioid peptides or by the inhibition or masking of mechanisms that reduce brain bioavailability significantly enhance the efficacy of opioid peptides for the treatment of pain.