[摘要]：agonists H-Dmt-Tic-Gly-NH-Ph and H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid (UFP-512) were evaluated for the influence of the substitution of Gly with aspartic acid, its chirality, and the importance of the -NH-Ph and N1H-Bid hydrogens in the inductions of d agonism. The results provide the following conclusions: (i) Asp increases d selectivity by lowering the m affinity; (ii) -NH-Ph and N1H-Bid nitrogens methylation transforms the d agonists into d antagonists; (iii) the substitution of Gly with L-Asp/D-Asp in the d agonist H-Dmt-Tic-Gly-NH-Ph gave d antagonists; the same substitution in the d agonist H-Dmt-Tic-NH-CH2-Bid yielded more selective agonists, H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid and H-Dmt-Tic-NH-(R)CH(CH2-COOH)-Bid; (iv) L-Asp seems important H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid(N1-Me) (I) evidenced analgesia similar to UFP-512, which was reversed by naltrindole only in the tail flick. UFP-512 and I had opposite behaviors in mice; UFP-512 caused agitation, I resulted in sedation and convulsions.
