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| In endomorphins (EMs), the C-terminal amide is an important element that can interact with opioid receptor directly. Presently, the antinociceptive effects of endomorphin-2 (EM-2) and its analogs with N-methylated modifications at C-terminus were determined using tail-flick test. The results indicated that both analogs 1 and 2 produced potent antinociceptive effects by a central opioid mechanism. At the dose of 20 nmol/kg, the maximal %MPE values of analogs 1 and 2 were 65.4 ± 4.0 and 57.8 ± 3.1, respectively, similar to that of EM-2 (60.1 ± 5.8). It was noteworthy that analog 1 showed a higher antinociceptive effect compared to EM-2, which would be helpful in the development of suitable μ-opioid therapeutics. Overall, the present results indicated that the N-methylated modifications of EM-2 C-terminus produced significant central antinociception, and N-methylation of C-terminus of EM-2 may play an important role in the regulation of antinociceptive effects. |
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| Keywords:pharmacology; endomorphin-2 analogs; opioid receptor; C-terminus; antinociception |
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