Effect of cyclic dipeptides containing histidine on pentobarbital narcosis

We examined the effect of cyclo (His-Pro) and its analogs on pentobarbital narcosis in mice. Cyclo (His-Pro), 500 nmol/mouse, administered via intracerebroventricular (i.c.v.) route significantly prolonged the sleeping time. Methylation of histidine in the structure of cyclo (His-Pro) did not increase the activity of cyclo (His-Pro). Some of other cyclo (His-Pro) analogs, of which proline was replaced with other amino acids, cyclo (His-Phe), cyclo (His-Tyr), cyclo (His-His) and cyclo (D-His-Leu) produced significant prolongation of the sleeping time as compared with cyclo (His-Pro). These results suggest that cyclo (His-Pro) has opposing effect to that of thyrotropin releasing hormone (TRH) and the prolongation of pentobarbital narcosis by cyclic dipeptides might be caused by their central action.