Long-lasting agonists of enkephalin

A method of treating pain comprising administering to a patient in need of such treatment, a therapeutically effective amount of a peptide of the formula:

• ##STR15## where, unless otherwise indicated, an amino acid substitutent identified below has the "S-" stereoconfiguration:
• X is S or (CH.sub.2).sub.n, where n is 0, 1 or 2;
• R.sub.1 is hydrogen;
• C.sub.1-6 alkyl;
• H-Arg;
• or H-Lys-Arg;
• R.sub.2 is hydrogen;
• C.sub.1-6 alkyl;
• or, when R.sub.1 is hydrogen, may be allyl or cyclopropylmethyl;
• R.sub.3 is hydrogen or methyl;
• R.sub.4 is benzyl;
• benzyl substituted with halo, nitro, hydroxy, amino, C.sub.1-4 alkyl, or cyano;
• indolylmethyl;
• imidazolylmethyl;
• or isopropylmethyl;
• R.sub.5 is hydrogen or methyl;
• R.sub.4 and R.sub.5 taken together are phenylmethylene;
• and
• R.sub.6 is (a) OM, where M is hydrogen, C.sub.1-6 alkyl, or a cation;
• (b) NR.sub.7 R.sub.8, where R.sub.7 and R.sub.8 are independently selected from the group consisting of hydrogen;
• C.sub.1-6 alkyl, and, when either of R.sub.7 or R.sub.8 is hydrogen, -CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2 and ##STR16## (c) Met-OH;
• (d) Met-NH.sub.2 ;
• (e) Met-ol;
• (f) D-Met-NH.sub.2 ;
• (g) N-methyl-Met-NH.sub.2 ;
• (h) Met(O)-NH.sub.2 ;
• (i) Met(O)-ol;
• (j) Leu-NH.sub.2 ;
• (k) N-methyl-Leu-NH.sub.2 ;
• (l) D-Leu-NH.sub.2 ;
• or (m) Pro-NH.sub.2.