RTI-336, (LS-193,309, (-)-2β-(3-(4-methylphenyl)isoxazol-5-yl)-3β-(4-chlorophenyl)tropane) is a phenyltropane derivative which acts as a potent and selective dopamine reuptake inhibitor and stimulant drug. It binds to the dopamine transporter with around 20x the affinity of cocaine, however it produces relatively mild stimulant effects, with a slow onset and long duration of action. These characteristics make it a potential candidate for treatment of cocaine addiction, as a possible substitute drug analogous to how methadone is used for treating heroin abuse. RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration, and significantly reduces rates of cocaine use, especially when combined with SSRIs, and research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.
Lower reinforcing strength of the phenyltropane cocaine analogs RTI-336 and RTI-177 compared to cocaine in nonhuman primates.
Influence of chronic dopamine transporter inhibition by RTI-336 on motor behavior, sleep and hormone levels in rhesus monkeys.
Pharmacotherapy for Cocaine Abuse
Development of the Dopamine Transporter Selective RTI-336 as a Pharmacotherapy for Cocaine Abuse (FIC, et al. 2006).
|RTI||X||R||[3H]CFT||[3H]Nisoxetine||[3H]Paroxetine||N ÷ D||S ÷ D|
|Coc||—||—||89.1||3298 (1986)||1045 (45)||37.01||11.79|
|177||Cl||phenyl||1.28||504 (304)||2420 (220)||393.8||1891|
|176||Me||phenyl||1.58||398 (239)||5110 (465)||251.9||3234|
|354||Me||ethyl||1.62||299 (180)||6400 (582)||184.6||3951|
|336||Cl||p-cresyl||4.09||1714 (1033)||5741 (522)||419.1||1404|
|386||Me||p-anisyl||3.93||756 (450)||4027 (380)||192.4||1025|