Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1984-02-23
1986-08-12
Phillips, Delbert R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530324, C07K 710, A61K 3724
Patent
active
046056424
ABSTRACT:
Several polypeptide analogs of the known members of the corticotropin releasing factor (CRF) family have been synthesized and tested including human and rat CRF which have the formula: H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val- Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu -Met-Glu-Ile-Ile-NH.sub.2. Peptides are herein disclosed that are potent competitive antagonists of CRF in mammals. One which has been found to be particularly potent is: H-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Met-Leu-Glu-Met-Ala-Lys-Ala-Glu- Gln-Glu-Ala-Glu-Gln-Ala-Ala-Leu-Asn-Arg-Leu-Leu-Leu-Glu-Glu-Ala-NH.sub.2. These antagonists or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, including humans, to achieve a prevent elevation of ACTH, .beta.-endorphin, .beta.-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels and/or a lowering of brain-mediated responses to stress over an extended period of time. They may also be used to affect mood, memory and learning, as well as diagnostically.
REFERENCES:
patent: 4415558 (1983-11-01), Vale et al.
"Characterization of a 41-Residue Ovine Hypothalamic Peptide that Stimulates Secretation of Corticotropin and .beta.-Endorphin"-Science, vol. 213, pp. 1394-1397.
Margioris et al., Endocrinology, 113(2), 663-671, 1983.
Rivier et al., Science, vol. 224, 889-891 (1984).
Gold et al., Am. J. Psychiatry, 619-627 (1984).
Stodman's Medical Dictionary, 23rd ed., The Williams and Wilkins Co., Baltimore, p. 1346.
Spiess et al., Proc. Natl. Acad. Sci. USA, vol. 78, No. 10, 1981, pp. 6517-6521.
Rivier et al., Endocrinology, vol. 110, No. 1, 1982, pp. 272-278.
Brown Marvin R.
Rivier Catherine L.
Rivier Jean E. F.
Vale, Jr. Wylie W.
Moezie F. T.
Phillips Delbert R.
The Salk Institute for Biological Studies
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