Study of the structural requirements for Dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide

Abstract

A number of analogs of the tripeptide L-prolyl-L-leucylglycinamide (1) were synthesized and evaluated in the dopa potentiation and oxotremorine antagonism tests in mice treated i.p. The replacement of the glycinamide residue with either the glycine methylamide, glycine, aminoacetonitrile, amino-2-propanone, semicarbazide or .beta.-alaninamide residues resulted in a loss of activity in both tests. A 1:1 mixture of L-prolyl-L-leucyl-(-)-thiazolidine-2-carboxamide and L-prolyl-L-lucyl-(+)-thiazolidine-2-carboxamide showed marked activity in the dopa potentiation test but was unable to antagonize the tremors induced by oxotremorine. L-Prolyl-L-leucyl-L-prolinamide was active in the oxotremorine antagonism test but inactive in the dopa potentiation test. The replacement of the pyrrolidine ring of 1 with either a thiazolidine or cyclopentane ring system caused a loss of activity. The cyclopentanecarboxylic acid analog had moderate activity in the serotinin potentiation test.