Low molecular weight
opioid peptide esters (OPE) could become a class of
analgesics with different side effect profiles than current
opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo
ester hydrolysis and produce
analgesia. OPE of
dipeptides,
tyr-pro and tyr-gly conjugated to
ethanol have a structure similar to the anesthestic agent,
etomidate. Based upon the
analgesic activity of
dipeptide opioids, Lipinski's criteria, and permeability of select
GABA esters to cross the BBB,
opioid peptides (OP) conjugated to
ethanol,
cholesterol or 3-glucose are lead recommendations. Preliminary animal data suggests that
tyr-pro-ethyl
ester crosses the BBB and unexpectedly produces
hyperalgesia. Currently, there are no approved OP
analgesics available for clinical use. Clinical trials of good manufacturing practice OP administered to patients suffering from
chronic pain with indwelling intrathecal pumps could resolve the issue that OP may be superior to
opiates and may redirect research.