Reversal of amnesia by an orally active ACTH 4-9 analog (Org 2766).

The ACTH 4-9 analog, H-Met((O2)-Glu-His-Ph-D-Lys-Phe-OH (Or 2766), attenuates in rats CO2-induced amnesia for a one-trial passive avoidance step-through response when administered prior to the retrieval test but not when given prior to acquisition. Even a dose of 0.001 mug/rat Org 2766 yields an anti-amnesic effect. In this respect Org 2766 is more active than the ACTH fragment ACTH 4-10. An anti-amnesic effect was also obtained when Org 2766 was administered orally. ACTH 4-10 (100 mug/rat) has to be given SC within 8 hr of the retrieval test in order to be effective. A similar time span of effectiveness was observed when Org 2766 was SC injected in a dose of 0.1 mug/rat. The anti-amnesic effect of ACTH 4-10 remains when the time interval between acquisition and retrieval is extended beyond the usual 24 hr. The same appeared to be true for SC ADMINISTERED Org 2766. It is suggested that ACTH-like peptides, and particularly the orally active Org 2766, may be helpful in the treatment of deficient mental performance.