RECEPTOR-BINDING PROPERTIES OF AMPEROZIDE

The receptor pharmacology of amperozide was investigated with in vitro radioligand binding technique. Amperozide possessed a high affinity to the 5‐HT2 receptors (Ki= 16.5±2.1 nM) and a moderate affinity to α1‐adrenergic receptors of rat cerebral cortical membranes (Ki=172±14 nM). The affinity of amperozide for striatal and limbic dopamine D2 receptors was low and not significantly different (Ki±S.E.M. = 540 ± 59 nM vs 403±42 nM; p<0.11, n = 4). The affinity for striatal and limbic 5‐HT2 receptors was measured as well and found to be very close to the affinity to the cerebral cortical 5‐HT2 receptor. The drug affinity for D2 and 5‐HT2 receptors seems thus not to be influenced by the location of the receptor moiety. The affinity for several other rat brain receptors such as 5‐HT1A, α2‐adrenergic, dopamine D1 muscarinic M1 and M2, opiate sigma and β2‐adrenergic was low. The pseudo‐Hill coefficient of the amperozide competition binding curve was consistently higher than one indicating antagonistic and complex interactions with the 5‐HT2 receptor or with α1‐adrenergic and dopamine D2 receptors. The antagonistic properties of amperozide were investigated by its ability to antagonize the serotonin‐induced formation of inositol‐1‐phosphate in human blood platelets. Amperozide inhibited this 5‐HT2 receptor‐mediated intracellular response with similar potency as ketanserin. These results suggest that amperozide is a selective 5‐HT2 receptor antagonist. 1990 Nordic Pharmacological Society