Conformationally constrained cyclic enkephalin analogs with delta receptor specificity

A pharmaceutical composition comprising an opioid receptor agonist having enhanced specificity for delta opioid receptors of the formula:

• ##STR56## wherein R.sup.1 and R.sup.2, which may be the same or different, are hydrogen, methyl, or a lower alkyl group having five or less carbon atoms;
• R.sup.3 and R.sup.4, which may be the same or different, are hydrogen, methyl, or lower alkyl groups having five or less carbon atoms, provided, however, that R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may not all be hydrogen;
• R.sup.5 is hydrogen, L-tryosine, D-tryosine, or D-tyrosine or L-tyrosine substituted on the N.sup..alpha. -amino with 1 or 2 lower alkyl or alkenyl groups;
• R.sup.6 is a substituted or unsubstituted aromatic radical;
• R.sup.7 is hydrogen or methyl;
• R.sup.8 is carboxylate, carboxamide or amino acid residue;
• X and Y are hydrogen or methyl;
• and
• n and m, which may be the same or different, are 0 or 1,
• or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier in a pharmaceutically acceptable amount.

A pharmaceutical composition comprising an opioid receptor agonist having enhanced specificity for delta opioid receptors of the formula:

• ##STR57## where:
• R.sup.1 and R.sup.2, which may be the same or different, are hydrogen, methyl, or lower alkyl having one to five carbon atoms;
• R.sup.3 and R.sup.4, which may be the same or different, are hydrogen, methyl, or lower alkyl having one to five carbon atoms, provided, however, that R.sup.1, R.sup.2, R.sup.3, and R.sup.4 may not al be hydrogen;
• R.sup.7 is hydrogen or methyl;
• R.sup.8 is carboxylate, carboxamide, or amino acid residue;
• X and Y are hydrogen or methyl;
• and,
• Z is hydrogen, nitro, fluoro, or amino,
• or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier, in a pharmaceutically acceptable amount.