Antinociceptive effects of [D-Ala²]deltorphin II, a highly selective δ agonist in vivo

The present study has characterized the antinociceptive actions of [D-Ala²]deltorphin II following intracerebroventricular (i.c.v.) administration in the mouse tail-flick test. [D-Ala²]deltorphin II produced dose- and time-related antinociception, with maximal effects at +10 min and significant antinociception which lasted for 40-60 min. [D-Ala²]deltorphin II was 13-fold more potent than i.c.v. [D-Pen², D-Pen⁵]enkephalin (DPDPE), a second highly selective δ agonist, and approximately equipotent with i.c.v. morphine in producing antinociception. The antinociceptive effects of i.c.v. [D-Ala²]deltorphin II and DPDPE, but not those of morphine, were antagonized by the selective δ antagonist, ICI 174,864. In contrast, pretreatment with the non-equilibrium μ antagonist, β-funaltrexamine blocked morphine antinociception, but failed to antagonize [D-Ala²]deltorphin II and DPDPE antinociception. These data indicate that [D-Ala²]deltorphin II produced its antinociceptive effects at a supraspinal δ receptor. [D-Ala²]deltorphin II appears to be the most appropriate δ opioid agonist currently available for studies in vivo and support the involvement of δ receptors in supraspinal antinociception.