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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Stereoselectivity of the Antidopaminergic Effect of the Methyl Ester of N-Caproylprolyltyrosine (I) -a Tripeptide Analogue of Neurotensin.-It is shown, that for an optimal antidopaminergic effect both amino acid residues of the title N-caproylprolyltyrosine (I) must have L-configuration. Changing one of the amino acids by its D-enantiomer results in loss of activity. N-Caproylprolyltyrosine containing D-prolyl and D-tyrosyl residues has a "pro-dopamine" effect. -(ZAITSEVA, N. I.; GUBASHEVA, T. A.; BRILING, V. K.; GUZEVATYKH, L. S.; OSTROVSKAYA, R. U.; VORONINA, T. A.; SEREDENIN, S. B.; Khim.-Farm. Zh. 34 (2000) 8, 20-22; Nauchno-issled. inst. farmakol. Ross. Akad. med. nauk, Moskva 125315, Russia; RU)