JJC8-088
Cocaine-like dopamine reuptake inhibitor derived from modafinil
From Wikipedia, the free encyclopedia
JJC8-088 is a dopamine reuptake inhibitor (DRI) that was derived from the wakefulness-promoting agent modafinil.[1][2][3]
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| Drug class | Typical dopamine reuptake inhibitor |
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| Formula | C28H32F2N2O2S |
| Molar mass | 498.63 g·mol−1 |
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It has substantially higher affinity for the dopamine transporter (DAT) than modafinil (Ki = 6.72 nM vs. 2,600 nM; 387-fold).[2] In contrast to modafinil and other analogues, which are atypical DRIs, JJC8-088 is a typical cocaine-like DRI.[1][3] It has potent cocaine-like psychostimulant effects, produces robust and dose-dependent increases in dopamine levels in the nucleus accumbens, and is readily self-administered by and substitutes for cocaine in animals.[1][3]
Similarly to cocaine, but unlike modafinil and other analogues, JJC8-088 stabilizes the DAT in an outward-facing open conformation.[1] It has been theorized that cocaine-like DRIs may actually act as dopamine releasing agent-like DAT "inverse agonists" rather than as simple transporter blockers.[4]
In addition to its affinity for the DAT, JJC8-088 has low affinity for the serotonin transporter (SERT) (Ki = 213 nM; 32-fold less than for the DAT) and for the norepinephrine transporter (NET) (Ki = 1950 nM; 290-fold less than for the DAT).[2] It also binds with high affinity to the sigma σ1 receptor (Ki = 41.6 nM).[5]
The drug has high affinity for the hERG antitarget (IC50 = 130 nM) and could produce cardiotoxicity,[6][7] which might cause a risk of heart attack if JJC8-088 were to be used recreationally.[8][9]