A series of N-acylprolyltyrosine amides was designed as tripeptoid analogues of neurotensin. The substituted dipeptides were tested in vivo for antidopamine activity by their ability to inhibit the apomorphine-induced climbing in mice and the dopamine-induced extrapolatory behavior impairment in rats. The N-acylprolyltyrosine amides structure-activity relationships have indicated the size of the N-acyl group and the configuration of amino acids that are important for the activity. We found that the bioactivity has been increased dramatically when the n-hydrocarbon chain on the N-acyl group was increased from four to five carbon atoms. The activity seems to reside exclusively in the L-Tyr diastereomers. All of the compounds tested were inactive in the cataleptogenic action and did not exhibit the acute toxicity even at doses 500-1000 times higher than ED50 in climbing test. On this basis, the N-acylprolyltyrosine amides could potentially be a novel class of atypical antipsychotic agents.

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The effects of wheat gluten fragments, hemoglobin, and milk B-caseins (exorphine C, hemorphine-6, and B-casomorphine-7) on nociceptive sensitivity and behavior were studied in albino rats. Hemorphine-6 and exorphine C induced hyperalgesia and increased anxiety; B-casomorphine-7 decreased anxiety and nociceptive sensitivity. All peptides partially decreased motor activity and the orientative-exploring reaction. In contrast to 13-casomorphine-7, exorphine C and hemorphine-6 did not exhibit neurotropic activity intrinsic to opioids and can be characterized as functional antagonists of endogenous opioid peptides.

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Design, Synthesis and Neuroleptic Activity of Dipeptide Analogues of Sulpiride. -Dipeptide analogues of sulpiride are prepared in order to study the influence of nature and configuration of the amino acids on the neuroleptic activity. The best results are obtained for the L-or D-prolyl-L-tyrosinamide (Ia) while the change of L-to D-tyrosine or to another amino acid (Ib) or (Ic) causes a loss of activity. -(GUDASHEVA, T. A.; ZAITSEVA, N. I.; BONDARENKO, N. A.; SHCHERBAKOVA, I. E.; ASMAKOVA, L. S.; ROZANTSEV, G. G.; OSTROVSKAYA, R. U.; VORONINA, T. A.; SEREDENIN, S. B.; Khim.-Farm.

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