Neurotensin-induced hypothermia in the rat: Structure-activity studies

Neurotensin (NT), an endogenous brain tridecapeptide, produces hypothermia after intracerebroventricular administration in rats and mice. The hypothermie potency of a series of structural analogues of neurotensin has been studied. [ d-Arg 9]-NT, NT 9–13 and physalemin were devoid of hypothermie activity. The most potent peptides studied in reducing body temperature of cold-exposed rats were bombesin and [ d-Tyr 11]-NT. [ d-Arg 8]-NT, [Phe 11]-NT, [ d-Pro 7]-NT, NT-MHMe [ d-Pro 10]-NT and NT 8–13 possessed significant hypothermie activity, though the latter two compounds were the least active. These results indicate that the C-terminal end of the neurotensin molecule is essential for hypothermie activity

Modification of pentobarbital-induced sedation by natural and synthetic peptides

The effect of intraperitoneal (i.p.) and intracisternal (i.e.) injection of various endogenous peptides and related analogues on the sedation induced by a fixed intraperitoneal dose of sodium pentobarbital in mice was examined. Several peptides were found to antagonize the effects of pentobarbital while one (neurotensin) markedly potentiated them. Certain peptides were active only after intracisternal injection, while others were effective by either route of administration. However, peptides active after intraperitoneal administration were always active after intracisternal administration. Thyrotropin-releasing hormone was the most effective antagonist and was active by both routes. Neurotensin was the most potent potentiator but was active only after central administration. Although few general structural requirements for the analeptic activity of peptides are discernable, it appears that such activity is mediated by the central nervous system