Identification of Alkaloids from W. T. Wang as Dopamine D₁ Receptor Antagonists by Using CRE-Luciferase Reporter Gene Assay.

W. T. Wang () has been traditionally used for drug addiction and pain relief in China. In our previous study, we showed that the extract of blocks dopamine receptors, demonstrating that its pharmacological activities are mostly due to the antagonistic effects of some of its components at dopamine receptors. As part of our ongoing project on , the aim of the present study is to establish a high-throughput and low-cost screening assay system and test the abilities of the isolated alkaloids from to inhibit dopamine-induced dopamine D₁ receptor activity. By using our established cyclic adenosine monophosphate (cAMP)-response element (CRE)-luciferase reporter gene assay system, we identified eight alkaloids from with D₁ receptor antagonistic activities. We next validated the activities of these compounds using fluorometric imaging plate reader (FLIPR) assay by measuring the intracellular Ca change. Six out of eight compounds, including tetrahydropalmatine, corydaline, 13-methyldehydrocorydalmine, dehydrocorybubine, dehydrocorydaline, and columbamine, can be confirmed for their inhibitory activities. The dopamine-receptor-antagonistic effects of four compounds, including 13-methyldehydrocorydalmine, dehydrocorydaline, columbamine, and corydaline, are reported for the first time. The present study provides an important pharmacological basis to support the traditional use of in China.