DPDPE (trifluoroacetate salt) (Synonyms: D-Pen2,D-Pen5Enkephalin)

DPDPE is a synthetic enkephalin peptide and δ-opioid receptor agonist (Ki = 2.7 nM in rat brain homogenates). DPDPE has greater than 250-fold selectivity for the δ-opioid receptor over the μ- and κ-opioid receptors in rat brain homogenates (Kis = 713 and >1,500 nM, respectively). It also selectively inhibits electrically-evoked contractions in mouse vas deferens over guinea pig myenteric plexus (IC50s = 4.14 and 3,000 nM, respectively), which does not express the δ-opioid receptor. In vivo, DPDPE (140 nmol, i.v.) completely blocks tonic hindlimb extension induced by maximal electroshock (MES) in 50% of tested rats and increases the flurothyl-induced seizure threshold by 15-20% in rats, effects that can be blocked by the selective δ-opioid receptor antagonist ICI 154129. DPDPE (1-10 μg, i.v) dose-dependently reduces formalin-induced paw licking and lifting, indicating analgesia, in rats. However, DPDPE (15 μg, i.v.) increases the latency to tail withdrawal in the tail-immersion test in both wild-type and δ-opioid receptor knockout mice by 6.74 and 7.6 seconds, respectively, compared to a saline control, but not in μ-opioid receptor knockout mice, and the effect can be blocked by the μ-opioid receptor antagonist CTOP.