Comparison of the affinities of amoxapine and loxapine for various receptors in rat brain and the receptor down-regulation after chronic administration].

H B Wei, X Y Niu

Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing.

Yao xue xue bao = Acta pharmaceutica Sinica 1990

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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.

Citation

H B Wei, X Y Niu. Comparison of the affinities of amoxapine and loxapine for various receptors in rat brain and the receptor down-regulation after chronic administration]. Yao xue xue bao = Acta pharmaceutica Sinica. 1990;25(12):881-5