Biologically stable analogues of trh with increased neuropharmacological potency

Two simple analogues of TRH containing a 3-methyl or 3,3-dimethyl substituted prolineamide residue have been studied. In CNS tests both analogues showed increased activity, the dimethyl analogue being the most potent. The potency changes observed correlated with the increased biological stability of the analogues against enzymes located in the brain and various peripheral tissues. It is concluded that the increased resistance to inactivation shown by the analogues is a major contributor to their enhanced potency.