Antinociceptive activity of deltorphin analogs in the formalin test.

Two deltorphin (DLT: Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) analogs, [N alpha-n-butyl-Gly6]DLT ([nBuG6]DLT) and [N alpha-iso-butyl-Gly6]DLT ([isoBuG6]DLT), were examined for their antinociceptive activities by a formalin test in mice after subcutaneous (s.c.) injection. [nBuG6]DLT exhibited potent dose-dependent antinociceptive activities at doses of more than 0.02 mumol/kg at the first and second phases, while morphine similarly inhibited of the pain responses at doses more than 0.01 mumol/kg in the formalin test. [isoBuG6]DLT showed potent antinociceptive activity at the second phase, but did not inhibit the pain response at the first phase. This phenomenon may be caused by a mu-antagonist/delta-agonist property of this compound. The antinociceptive effects of these analogs were antagonized by delta-antagonist naltrindole, but not by the mu-antagonist naloxone. These findings suggest that the antinociceptive effects were mediated via delta-receptors. These compounds may be useful as delta-agonists for clarifying the mechanism of analgesia mediated by delta-opioid receptors.