Effect of YM-09151-2, a putative D2 dopamine receptor antagonist, on dopamine metabolism in the striatum of rats.
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 (homovanillic 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.
Shibanoki
S
S
Department of Pharmacology, Nihon University School of Medicine, Tokyo, Japan.
Kubo
T
T
Imamura
Y
Y
Asai
S
S
Ishii
Y
Y
Tada
K
K
Ishikawa
K
K
D000818:Animals; D014150:Antipsychotic Agents; D001549:Benzamides / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
D014150:Antipsychotic Agents; D001549:Benzamides; D011954:Receptors, Dopamine; C030265:nemonapride; D004298:Dopamine