Abstract: Using radioligand receptor binding methods, the affinities (K_i) of amoxapine and loxapine for various receptors (adrenergic α₁, α₂, β, dopaminergic D₁, D₂; serotoninergic 5-HT₁, 5-HT₂; Muscarinic, GABA, BZ) were investigated. The two compounds showed high affinities for 5-HT₂, D₂ and α₁ receptors (K_i<10^-7 mol/L), moderate affinity for α₂ receptor (K_i<10^-6 mol/L), and low affinities for M and 5-HT₁ receptor (K_i<10^-5 mol/L). In addition, amoxapine appeared to have low affinities for D₁ and GABA receptors. For D₁ receptor, loxapine was found to have moderate affinity which was nearly 20 fold greater than amoxapine, but amoxapine exhibited more potent inhibitory effects on serotonin receptors and weaker inhibitory affects on dopamine receptors. Neither amoxapine nor loxapine showed siginificant effinity for BZ and β-adrenergic receptors. These differencesin the affinities may be responsible for their different psychopharmacological effects in the clinical treatment of patients. The regulation of 5-HT₂ and β receptors were examined in chronic experiments on rats given amoxapine 8mg/kg or loxapine 1mg/kg orally once daily for one to three weeks. The 5-HT₂ receptor density was time-dependently reduced but no effect on receptors was observed. The down-regulation of 5-HT₂ receptors might be associated with antidepressant action of the two drugs.