201. [Biological activity of cholecystokinin-(30-33) tetrapeptide analogs].
- Author
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Proskuriakova TV, Bespalova ZhD, Pal'keeva ME, Petrichenko OB, Pankratova NV, Shokhonova VA, and Anokhina IP
- Subjects
- Analgesics chemical synthesis, Analgesics pharmacology, Animals, Anti-Anxiety Agents chemical synthesis, Anti-Anxiety Agents pharmacology, Anxiety chemically induced, Brain metabolism, Drug Synergism, In Vitro Techniques, Morphine pharmacology, Oligopeptides pharmacology, Pancreas metabolism, Radioligand Assay, Rats, Rats, Wistar, Receptor, Cholecystokinin A metabolism, Receptor, Cholecystokinin B metabolism, Structure-Activity Relationship, Tetragastrin pharmacology, Tryptophan chemistry, Alcohol Drinking drug therapy, Behavior, Animal drug effects, Oligopeptides chemical synthesis, Tetragastrin analogs & derivatives, Tetragastrin chemical synthesis
- Abstract
Analogues of the endogenous peptide corresponding to the 30-33 sequence of cholecystokinin (Trp-Met-Asp-Phe-NH2) were synthesized, and their biological activity was studied. It was shown that, in rats, the N-succinylated Nle2 analogue of this tetrapeptide exhibits increased anxiolytic properties in the dark-bright chamber test and an enhanced alcohol intake by both the control animals and the long-time alcohol-dependent animals under the conditions of free choice. Introduction of an isopropyl residue into the C-terminal amide of the Nle2 analogue resulted in the appearance of anxiolytic and antialcohol activity and the ability to increase the morphine analgesic effect in the tail-flick test on rats. The two synthesized analogues retained an affinity to cholecystokinin receptors.
- Published
- 2005