Unusual binding of [3H] MDL 72222 in guinea pig hippocampus

[3H] MDL 72222 labeled a non-homogeneous population of sites in guinea pig hippocampal membranes (Kd1 = 1 nM; Kd2 = 60 nM). The binding was not sodium dependent. Competition studies with a variety of characterizing agents showed displacement of [3H] MDL 72222 binding by 5-HT uptake inhibitors. [3H] MDL 72222 binding was not effectively displaced by established 5-HT3 antagonists. MDL 72222, fluoxetine, fluvoxamine and citalopram competitively inhibited the uptake of [3H] 5-HT into guinea pig hippocampal synaptosomes with Ki values of 1.97, 0.02, 0.023, 0.049 μM, respectively. The results demonstrate that [3H] MDL 72222 labels a non-homogeneous population of sites in guinea pig brain, as well as inhibiting 5-HT uptake into synaptosomal preparations.