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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.
Open accessAbstract
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.
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Citations
Cited by
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Metadata
- Authors
- Kikuchi, T., Tottori, K., Uwahodo, Y., Hirose, T., Miwa, T., Oshiro, Y., & Morita, S.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1995-07
- Volume
- 274
- Issue
- 1
- Pages
- 329-336
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1944617386
- Cited by
- 276
- References
- 0
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: 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. https://app.cochat.ai/papers/10.1016/s0022-3565(25)10600-9
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- Kikuchi, T., Tottori, K., Uwahodo, Y., Hirose, T., Miwa, T., Oshiro, Y., & Morita, S. (1995). 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 Journal of Pharmacology and Experimental Therapeutics. https://doi.org/10.1016/s0022-3565(25)10600-9
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