org-2766 and ebiratide

Clinical studies of cognitive effects of ACTH fragments carried out so far with ACTH (1-10) and (4-9) (Org. 2766) brought about inconsistent and partly disappointing results. Efficacy could not be demonstrated in patients with Alzheimer's disease (AD). A possible reason for these results is the low metabolic stability and low lipophilicity of these compounds. HOE 427 has a considerably prolonged metabolic stability, has a high lipophilicity, and is much more potent than are existing compounds in pharmacologic models of memory and learning. It also was proven to have significant effects on ACh metabolism. Single dose studies in groups of mildly cognitively impaired elderly subjects and in patients with AD showed slight but significant effects on attention and mood. The effects were less consistent in patients than in healthy subjects.

Topics: Adrenocorticotropic Hormone; Affect; Alzheimer Disease; Animals; Cognition; Double-Blind Method; Humans; Peptide Fragments; Rats

Clinical studies of cognitive effects of ACTH fragments carried out so far with ACTH (1-10) and (4-9) (Org. 2766) brought about inconsistent and partly disappointing results. Efficacy could not be demonstrated in patients with Alzheimer's disease (AD). A possible reason for these results is the low metabolic stability and low lipophilicity of these compounds. HOE 427 has a considerably prolonged metabolic stability, has a high lipophilicity, and is much more potent than are existing compounds in pharmacologic models of memory and learning. It also was proven to have significant effects on ACh metabolism. Single dose studies in groups of mildly cognitively impaired elderly subjects and in patients with AD showed slight but significant effects on attention and mood. The effects were less consistent in patients than in healthy subjects.

Topics: Adrenocorticotropic Hormone; Affect; Alzheimer Disease; Animals; Cognition; Double-Blind Method; Humans; Peptide Fragments; Rats

The behavioral effects of two peptides (HOE 427) and ORG 31433) related to the ACTH-(4-9) analog ORG 2766 were investigated in Wistar rats in a number of tests in which Org 2766 is active. Subcutaneous administration of HOE 427 in a dose of 0.5 ng/kg or ORG 31433 in doses of 0.5-5.0 ng/kg facilitated passive avoidance behavior whereas these peptides attenuated the avoidance response in doses of 25 ng/kg and 250 ng/kg respectively. ORG 31433 (0.1 - 1.0 microgram/kg) decreased motor activity of group housed rats tested under low light conditions. Furthermore subcutaneous (1.0- 10.0 ng/kg) or oral (10 microgram/kg) administration of ORG 31433 accelerated functional recovery from 6-hydroxydopamine (6-OHDA)-induced lesions in the nucleus accumbens which cause motor hypoactivity. The experiments show that as compared to ORG 2766 the peptides HOE 427 and ORG 31433 induce qualitatively similar responses but are approximately 10 to 100 times more potent. These data may imply that substitution of the C-terminal COOH group of ORG 2766 yields neuropeptides with increased potency.

Topics: Administration, Oral; Adrenocorticotropic Hormone; Animals; Anticonvulsants; Behavior, Animal; Dose-Response Relationship, Drug; Hydroxydopamines; Injections, Subcutaneous; Male; Motor Activity; Nucleus Accumbens; Oxidopamine; Peptide Fragments; Rats; Rats, Inbred Strains