further studies on lead compounds containing the opioid pharmacophore dmttic some reference opioids containing the dmttic pharmacophore especially the delta agonists hdmtticglynhph 1 and hdmtticnhschch2coohbid 4 ufp512 were evaluated for the influence of the substitution of gly with aspartic acid its chirality and the importance of the nhph and n1hbid hydrogens in the inductions of delta agonism the results provide the following conclusions i asp increases delta selectivity by lowering the mu affinity ii nhph and n1hbid nitrogens methylation transforms the delta agonists into delta antagonists iii the substitution of gly with laspdasp in the delta agonist hdmtticglynhph gave delta antagonists the same substitution in the delta agonist hdmtticnhch2bid yielded more selective agonists hdmtticnhschch2coohbid and hdmtticnhrchch2coohbid iv lasp seems important only in functional bioactivity not in receptor affinity v hdmtticnhschch2coohbidn1me 10 evidenced analgesia similar to 4 which was reversed by naltrindole only in the tail flick 4 and 10 had opposite behaviours in mice 4 caused agitation 10 gave sedation and convulsions