Effect of New Synthetic Analogs of Somatostatin on Gastric Secretion in the Chronic Fistula Dog

Summary

Somatostatin is a potent inhibitor of pentagastrin-evoked gastric secretion in the dog. Exploration of some of the structural requirements for antisecretory activity in this species has revealed that potency in reducing T.A.O. has been retained in compounds wherein alanine (Ala 1 ) and glycine (Gly 2 ) and the amino and carboxyl groups of terminal cysteine^3'14, have been omitted. Locking the ring structure by replacing the sulfur with carbon retained activity. Compared to somatostatin, the active analogs (des-(Ala 1 , Gly 2 )-desamino-Cys 3 -somatos-tatin, des-(Ala 1 , Gly 2 )-desamino-Cys 3 -dicar-basomatostatin, and des-(Ala 1 , Gly 2 )-desa-mino-Cys 3 -decarboxy-dicarbasomatostatin) were slightly less effective in reducing the concentration of acid secreted.

We thank Dr. N. R. Bohidar for statistical analysis. The somatostatin derivatives were prepared under the direction of Dr. R. F. Hirschmann by Drs. F. W. Holly and D. F. Veber and Messrs. M. J. Paleveda and R. G. Strachan. Insulin (RIA) determinations were made by Dr. R. Saperstein, Merck Institute, Rahway, N. J.