Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Kikuchi, T. et al.

7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity.

The effects of 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2 (1H)- quinolinone (OPC-14597), a derivative of the dopamine (DA) autoreceptor agonist 7-(3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy)-2(1H)-quinolinone (OPC-4392), on DA receptors were biochemically and behaviorally studied and compared with those of OPC-4392. Both OPC-14597 and OPC-4392 inhibited reserpine- and gamma-butyrolactone (GBL)-induced increase in tyrosine hydroxylase activity in the mouse and rat brain. The effects of OPC-14597 were comparable to those of OPC-4392 and were completely antagonized by haloperidol. OPC-14597, unlike apomorphine, did not evoke postsynaptic DA receptor-stimulating behavioral signs such as hyperlocomotion in the reserpinized mice and contralateral rotation in rats with unilateral striatal 6-hydroxydopamine lesions. Both OPC-14597 and OPC-4392 inhibited such apomorphine-induced postsynaptic behavioral changes as stereotypy and hyperlocomotion in mice and rats and rotation in rats with unilateral striatal kainic acid lesions. The anti-apomorphine effects of OPC-14597 were about 30 to 140 times greater than those of OPC-4392 and were observed at doses that inhibit the increases in tyrosine hydroxylase activity. The affinities of OPC-14597 for 3H-spiperone-labeled D2 receptors in the rat frontal cortex, limbic forebrain and striatum were higher than those of OPC-4392. These results suggest that OPC-14597 is a unique antipsychotic drug candidate, being a DA autoreceptor agonist that has a stronger postsynaptic D2 receptor antagonistic activity than that of OPC-4392.[1]

References

7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity. Kikuchi, T., Tottori, K., Uwahodo, Y., Hirose, T., Miwa, T., Oshiro, Y., Morita, S. J. Pharmacol. Exp. Ther. (1995) [Pubmed]

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