JHW-007 is a cocaine analogue 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 psychostimulant 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]
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| Formula | C24H29F2NO |
| Molar mass | 385.499 g·mol−1 |
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Atypical dopamine reuptake inhibition
editIn 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
edit- ^ a b c d Avelar AJ, Cao J, Newman AH, Beckstead MJ (September 2017). "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. PMC 5546153. PMID 28625719.
- ^ Velázquez-Sánchez C, Ferragud A, Murga J, Cardá M, Canales JJ (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. PMID 20413276. S2CID 21330820.