PHARMACOLOGICAL CHARACTERIZATION AND AUTORADIOGRAPHIC DISTRIBUTION OF POLYAMINE-SENSITIVE [H-3] IFENPRODIL BINDING-SITES IN THE RAT-BRAIN

Saturation studies with [H-3]ifenprodil (in the presence of 3-mu-M (+)-3-PPP and 10-mu-M GBR 12909) demonstrated the presence of a high-affinity (K(d) = 0.45-mu-M) population of binding sites in sagittal rat brain sections. This binding was inhibited by spermine (IC50 = 69-mu-M) and spermidine (IC50 = 623-mu-M) but not by putrescine (1 mM). Ifenprodil displaced this binding in a biphasic fashion with a high affinity component (IC50 = 0.992-mu-M) accounting for approximately 50% of the spermine-displaceable [H-3]ifenprodil binding. The polyamine-sensitive [H-3]ifenprodil binding sites were heterogenously distributed in the rat brain, the highest binding densities being found in the hippocampus and in the nucleus accumbens. The anatomical distribution of [H-3]ifenprodil binding sites closely matches that previously reported for the N-methyl-D-aspartate (NMDA) receptor.