Conformationally restricted analogs of somatostatin with high mu-opiate receptor specificity.

Abstract
A series of cyclic, conformationally restricted analogs of somatostatin were prepared and tested for their ability to inhibited the binding of [3H]naloxone and [D-Ala2, D-Leu5][3H]enkephalin to rat brain membranes. The most potent analog is given; it exhibited high affinity for .mu.-opiate receptors (IC50 [mean inhibitory concentration] value of [3H]naloxone = 3.5 nM), being 7800 times more petent than somatostatin. The cyclic octapeptide also displayed high .mu.-opiate receptor selectivity with an IC50 ([D-Ala2, D-Leu5]enkephalin)/IC50 (naloxone) ratio of 271. The high affinity and selectively of the somatostatin analog for .mu.g-opiate receptors may be of use in examining the physiological role(s) of the .mu.-opiate receptor.