THE NONPEPTIDE NEUROTENSIN RECEPTOR ANTAGONIST SR48692 IS NOT A POTENT ANTAGONIST OF NEUROTENSIN(8-13) RESPONSES OF RAT SUBSTANTIA-NIGRA NEURONS IN-VITRO

The pharmacology of the neurotensin response of dopamine-sensitive neurons in the substantia nigra compacta was examined by testing the effect of a novel neurotensin receptor antagonist, SR48692, on the response to neurotensin(8-13). Extracellular recordings of action potentials from neurons were made from coronal rat brain slices maintained in vitro. SR48692 was unable to antagonise the actions of neurotensin(8-13) until mu M concentrations were applied. The equilibrium constant for SR48692 was 4.9 mu M compared with low nM K-i values reported in binding experiments. The data suggests that the pharmacology of the neurotensin response in the rat substantia nigra may be different to that predicted from radioligand-binding studies in cell lines and brain homogenates.