Chemistry:JHW-007
JHW-007 is a cocaine analog and a high affinity atypical dopamine reuptake inhibitor that is being researched for the treatment of cocaine addiction. JHW-007 has been found to blunt the psychostimulatory effects of cocaine and reduce self-administration in rodents.[1] JHW-007 exposure has been shown to block the conditioned place preference effects of cocaine.[2] JHW-007 may directly antagonize the autoregulatory dopamine D2 receptor, a hypothesis that was developed following the observation of JHW-007's ability to inhibit D2 receptor-mediated currents in the midbrain.[1]
Atypical dopamine reuptake inhibition
In contrast to cocaine and other cocaine-like dopamine reuptake inhibitors, JHW-007 binds to the dopamine transporter (DAT) in an occluded (closed) conformation, similar to R-modafinil.[1] This type of receptor binding to the DAT has been observed to result in a gradual and sustained increase in extracellular dopamine in the nucleus accumbens. Peak levels of extracellular dopamine are also markedly reduced. Both modafinil and JHW-007 have been investigated for the treatment of cocaine addiction.[1]
References
- ↑ 1.0 1.1 1.2 1.3 Avelar, Alicia J.; Cao, Jianjing; Newman, Amy Hauck; Beckstead, Michael J. (2017-09-01). "Atypical dopamine transporter inhibitors R-modafinil and JHW 007 differentially affect D2 autoreceptor neurotransmission and the firing rate of midbrain dopamine neurons". Neuropharmacology 123: 410–419. doi:10.1016/j.neuropharm.2017.06.016. ISSN 1873-7064. PMID 28625719.
- ↑ Velázquez-Sánchez, C.; Ferragud, A.; Murga, J.; Cardá, M.; Canales, J. J. (July 2010). "The high-affinity dopamine uptake inhibitor, JHW 007, blocks cocaine-induced reward, locomotor stimulation, and sensitization". European Neuropsychopharmacology 20 (7): 501–508. doi:10.1016/j.euroneuro.2010.03.005. ISSN 1873-7862. PMID 20413276. https://pubmed.ncbi.nlm.nih.gov/20413276/.
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