A C-TERMINAL CYCLIC-8-13 NEUROTENSIN FRAGMENT ANALOG APPEARS LESS EXPOSED TO NEPRILYSIN WHEN IT CROSSES THE BLOOD-BRAIN-BARRIER THAN THE CEREBROSPINAL FLUID-BRAIN BARRIER IN MICE

A C-terminal cyclic 8-13 neurotensin fragment analog, JMV 1193, a dire ct agonist of central neurotensin receptors, is able to cross both the cerebrospinal fluid-brain barrier and the blood-brain barrier. When a dministered intracerebroventricularly (i.c.v.), its hypothermic effect was potentiated by the enkephalinase inhibition induced either by thi orphan (simultaneous intracerebroventricular administration of 10 mu g ) or by the thiorphan prodrug, acetorphan (intravenous (i.v.) administ ration of 10 mg/kg). Such a potentiation was not observed when both JM V 1193 and acetorphan were administered intravenously. Therefore it ap pears that the sensitivity of JMV 1193 to enkephalinase depends on its route of administration. It is exposed to this peptidase after i.c.v. injection (when crossing the cerebrospinal fluid-brain barrier), whil e it is not after i.v. administration (when crossing the blood-brain b arrier).