异戊塞平和克塞平对大鼠脑内各受体亲和力的比较及慢性给药后的受体下调作用

用放射配体受体结合法测定表明:克塞平对多巴胺D₁受体的亲和力较异戊塞平高近20倍。两药对其它各受体的亲和力差別不大。慢性给药后,异戊塞平和克塞平均能使大鼠脑皮层5-HT₂受体的密度显著下降,而亲和力变化不明显。这种下调5-HT₂受体的作用发生在给异戊塞平后1～2周之间,给克塞平后的2～3周之间。慢性给药3周,异戊塞平和克塞平均未使大鼠脑皮层的β受体密度及亲和力产生显著变化。

COMPARISON OF THE AFFINITIESOF AMOXAPINE AND LOXAPINE FOR VARIOUS RECEPTORS IN RAT BRAIN AND THE RECEPTOR DOWN-REGULATION AFTER CHRONIC ADMINISTRATION

Using radioligand receptor binding methods, the affinities (Ki) of amoxapine and loxapine for various receptors (adrenergic alpha 1, alpha 2, beta; dopaminergic D1, D2; serotoninergic 5-HT1, 5-HT2; Muscarinic, GABA, BZ) were investigated. The two compounds showed high affinities for 5-HT2, D2 and alpha 1 receptors (Ki less than 10(-7) mol/L), moderate affinity for alpha 2 receptor (Ki less than 10(-6) mol/L), and low affinities for M and 5-HT1 receptor (Ki less than 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 significant affinity for BZ and beta-adrenergic receptors. These differences in the affinities may be responsible for their different psychopharmacological effects in the clinical treatment of patients. The regulation of 5-HT2 and beta receptors were examined in chronic experiments on rats given amoxapine 8 mg/kg or loxapine 1 mg/kg orally once daily for one to three weeks. The 5-HT2 receptor density was time-dependently reduced but no effect on beta receptors was observed. The down-regulation of 5-HT2 receptors might be associated with antidepressant action of the two drugs.