Effect of YM-09151-2, a putative D2 dopamine receptor antagonist, on dopamine metabolism in the striatum of rats

Add time:07/29/2019    Source:sciencedirect.com

YM-09151-2, a novel benzamide derivative, significantly increased the concentrations of dopamine (DA) metabolites, both 3,4-dihydroxyphenylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid (honovanillic acid). The maximum increase in such metabolites was about 4-fold the concentration in control animals, and was observed at 2 hr after oral administration. 3-Methoxy-4-hydroxyphenylethylene glycol, a metabolite of noradrenaline, was slightly increased in its concentration exhibiting a transient effect, but 5-hydroxyindoleacetic acid was not. YM-09151-2 antagonized the decreasing effects of apomorphine, a nonselective DA agonist, and LY-171555, a selective D2 DA receptor agonist, on the concentrations of DA metabolites in the brain. In contrast, SCH-23390, a selective D1 DA receptor antagonist, did not antagonize the effects of DA agonist. These results strongly suggest that YM-09151-2 is a selective antagonist of D2 DA receptor and a candidate as a new antipsychotic agent for clinical use.

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