The non-peptide neurotensin receptor antagonist SR48692 is not a potent antagonist of neurotensin(8–13) responses of rat substantia nigra neurones in vitro

Abstract 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 μM concentrations were applied. The equilibrium constant for SR48692 was 4.9 μM 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.