Amperozide influences feeding independently of 5-HT2A receptor antagonism

Amperozide has been biochemically classified as a selective 5-HT2A (serotonin type 2A) receptor antagonist. However, research on the behavioral effects of amperozide suggests the possibility of other mechanisms. The present study in the male rat is an investigation of the effect of amperozide on feeding, a behavior which can be inhibited by 5-HT2A agonists such as 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Experiments revealed that amperozide acted to inhibit feeding behavior both when administered alone and when administered in combination with DOI. These results are inconsistent with 5-HT2A receptor antagonism by amperozide. Further experiments suggested that amperozide may be acting via alpha 2-adrenergic or 5-HT1A receptors to inhibit feeding. These studies imply that amperozide's selective 5-HT2A antagonistic activity is behaviorally specific.