STRUCTURE-ACTIVITY ANALYSIS OF THE MOTOR EFFECTS OF NEUROPEPTIDE-Y

The purpose of the present study was to examine structure-activity rel ationships for three known motor effects of neuropeptide Y (NPY): decr eased spontaneous activity, enhancement of muscle tone, and catalepsy. Various NPY fragments and structural analogues were synthesized and a dministered intracerebroventricularly in several doses (2.5-160 mu g); their effects on these three motor variables were evaluated and compa red. Globally, results indicate that the C-terminal portion of the pep tide is responsible for the three motor effects of NPY. However, the d istributions of potencies of the various fragments and analogues for e ach effect were clearly different, suggesting that the putative recept ors mediating each motor effect are pharmacologically different. The f indings of the present work are discussed in relation to those obtaine d in previous structure-activity studies.