Receptor binding properties of amperozide

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Abstract
The receptor pharmacology of amperozide was investigated with in vitro radioligand binding technique. Amperozide possessed a high affinity to the 5‐HT2receptors (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 D2receptors was low and not significantly different (Ki±S.E.M. = 540 ± 59 nM vs 403±42 nM; p2receptors was measured as well and found to be very close to the affinity to the cerebral cortical 5‐HT2receptor. The drug affinity for D2and 5‐HT2receptors 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 D1muscarinic 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‐HT2receptor or with α1‐adrenergic and dopamine D2receptors.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‐HT2receptor‐mediated intracellular response with similar potency as ketanserin.These results suggest that amperozide is a selective 5‐HT2receptor antagonist.