Analgesic/μ- & δ-opioids: Co-Administration of μ- and δ-Opioid Agonists Reduces the Side-Effects of the μ-opioid Agonist

Summary

Novelty: A combination of a μ-opioid agonist (opiate) and a δ-opioid agonist (enkephalin derivative) is disclosed, which shows potentiation of the analgesic, sedative, antitussive, and gastrointestinal motility modalities of opiate action, with a claimed reduction of tolerance and dependence.

Biology: Dose-response data for antinociceptive activity (hot plate trial) for the opiate/enkephalin combination are presented showing a significant and useful leftward shift in the presence of the enkephalin. For example, the ED₅₀ for morphine alone was 1.0 nmol upon intracerebroventricular (KK) administration and was 0.2 nmol in combination with 1.5 nmol DPDPE. Naloxone-precipitated dependence symptoms are not potentiated, though still present.

Chemistry: Preferred opiates are morphine, oxymorphine, codeine, methadone etc. Preferred enkephalins are [D-Pen², D-Pen⁵] enkephalin (DPDPE) and [D-Pen², L-Pen⁵] enkephalin (DPLPE).