Pure somatostatin antagonist and methods of use thereof

A method for decreasing the effect of somatostatin which comprises contacting the somatostatin receptor site with an effective amount of a peptide of formula I ##STR16## wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1 -C.sub.8 alkyl, COR or COOR;

• AA.sub.1 is the D or L isomer of an aromatic .alpha.-amino acid of formula II ##STR17## wherein Ar represents a moiety selected from the group consisting of ##STR18## wherein n is 0, 1, 2, or 3 and each substituent Y independently represents NO.sub.2, CN, Cl, Br, I, F, COR.sub.3, COOR.sub.3 or OR.sub.3 groups;
• AA.sub.2 is the D or L isomer of an aromatic .alpha.-amino acid of formula IIa ##STR19## wherein X is H, Ar and n are as defined above, and each substituent Y independently represents NO.sub.2, CN, Cl, Br, I, F, COR.sub.4, COOR, or OR4 groups;
• AA.sub.3 is the D or L isomer of Arg, Lys, Orn or Cit;
• AA.sub.4 is Val, Leu, Ile, Abu, Nle, Thr, 3-R5-Ser, Thr(Bzl) or Ser(Bzl), with the proviso that when AA.sub.4 is Thr, then AA.sub.1 must be the L isomer;
• AA.sub.5 is the, D or L isomer of an aromatic .alpha.-amino acid of formula Ia wherein X is H, Ar and n are as defined above, and each substituent Y independently represents NO.sub.2, CN, Cl, Br, I, F, COR.sub.6, COOR.sub.6 or OR.sub.6 groups, N(CH.sub.3)Ala, N(R.sub.7)-.alpha.-amino acid, Thr or Ser, with the proviso that the number of D-amino acid residues within the cyclic portion of the peptide is an even number;
• R is C.sub.1 C.sub.8 alkyl, phenyl, phenyl(C.sub.1 -C.sub.4)alkyl;
• naphthyl, or naphthyl(C.sub.1 -C.sub.4)alkyl;
• R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7 are each independently H or C.sub.1 -C.sub.8 alkyl;
• and
• R.sub.5 is H, C.sub.1 -C.sub.8 alkyl, or the D or L isomer of an aromatic .alpha.-amino acid of formula IIa wherein X is H, Ar and n are as defined above, and each substituent Y independently represents NO.sub.2, CN, Cl, Br, I, F, COR.sub.6 or OR.sub.6 groups;
• or
• the pharmaceutically acceptable salts thereof.