Neurotensin is a thirteen amino acid endogenous peptide, first discovered in the brain about thirty-five years ago. Evidence suggests that neurotensin is involved with neuropsychiatric disease, including schizophrenia and Alzheimer's disease. There are also data to suggest that it plays a role in the pathophysiology of Parkinson's disease and that it may be involved in some of the behavioral effects of psychostimulants (e.g., cocaine). From our research and that of others, we know that neurotensin and its binding sites are high in parts of the brain involved with movement (extrapyramidal system) and with emotional behaviors (limbic system).

Neurotensin causes a large number of behavioral effects when it is injected into animals. When given peripherally, neurotensin causes hypotension (therefore, the name neurotensin), vasodilation, and muscle relaxation. Because it is rapidly broken done by enzymes (peptidases) and because the so-called "blood-brain barrier" prevents its entry into brain, researchers have needed to inject neurotensin directly into brain to test its effects on brain function and behavior. When injected into the brain alone or after pretreatment with other drugs, neurotensin causes changes associated with the effects of extracranially-administered antipsychotic drugs (neuroleptics). For example, like neuroleptics, neurotensin injected into the brain causes hypothermia; blocks some behavioral effects of sympathomimetics such as d-amphetamine; and prolongs sleep after barbiturates. These and other results led to the suggestion by Dr. Nemeroff and colleagues that neurotensin is an endogenous, neuroleptic-like peptide. In addition, neurotensin is more potent than morphine in animal experiments testing pain perception. For nearly 25 years, our laboratory has focused on neurotensin and its receptors. The ultimate goal of this research is to develop drugs that act at stimulating neurotensin receptors in brain. These drugs could be of potential benefit to patients with schizophrenia, Parkinson's disease, or those who are abusing psychostimulants. As the result of modifications to the 8-13 fragment of neurotensin, which exhibits all the same activity as the 13-mer, we have obtained a number of stable compounds that penetrate into brain. Data published over the past few years with one particular compound (NT69L) do support the potential clinical uses of a neurotensin receptor agonist mentioned above. The research involves the disciplines of organic chemistry, pharmacology, biochemistry, molecular biology, and behavioral pharmacology.