RTI(-4229)-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,[1] however it produces relatively mild stimulant effects, with a slow onset and long duration of action.[2] (however other sources class it as having among the faster onsets of action from among phenyltropanes[3]) 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.[4][5] RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration,[6][7] and significantly reduces rates of cocaine use, especially when combined with
SSRIs,[8] and research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.
^Carroll FI, Pawlush N, Kuhar MJ, Pollard GT, Howard JL (January 2004). "Synthesis, monoamine transporter binding properties, and behavioral pharmacology of a series of 3beta-(substituted phenyl)-2beta-(3'-substituted isoxazol-5-yl)tropanes". Journal of Medicinal Chemistry. 47 (2): 296–302.
doi:
10.1021/jm030453p.
PMID14711303.
^Carroll FI, Fox BS, Kuhar MJ, Howard JL, Pollard GT, Schenk S (December 2006). "Effects of dopamine transporter selective 3-phenyltropane analogs on locomotor activity, drug discrimination, and cocaine self-administration after oral administration". European Journal of Pharmacology. 553 (1–3): 149–56.
doi:
10.1016/j.ejphar.2006.09.024.
PMID17067572.
^Howell LL, Carroll FI, Votaw JR, Goodman MM, Kimmel HL (February 2007). "Effects of combined dopamine and serotonin transporter inhibitors on cocaine self-administration in rhesus monkeys". The Journal of Pharmacology and Experimental Therapeutics. 320 (2): 757–65.
doi:
10.1124/jpet.106.108324.
PMID17105829.
S2CID9205978.
RTI(-4229)-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,[1] however it produces relatively mild stimulant effects, with a slow onset and long duration of action.[2] (however other sources class it as having among the faster onsets of action from among phenyltropanes[3]) 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.[4][5] RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration,[6][7] and significantly reduces rates of cocaine use, especially when combined with
SSRIs,[8] and research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.
^Carroll FI, Pawlush N, Kuhar MJ, Pollard GT, Howard JL (January 2004). "Synthesis, monoamine transporter binding properties, and behavioral pharmacology of a series of 3beta-(substituted phenyl)-2beta-(3'-substituted isoxazol-5-yl)tropanes". Journal of Medicinal Chemistry. 47 (2): 296–302.
doi:
10.1021/jm030453p.
PMID14711303.
^Carroll FI, Fox BS, Kuhar MJ, Howard JL, Pollard GT, Schenk S (December 2006). "Effects of dopamine transporter selective 3-phenyltropane analogs on locomotor activity, drug discrimination, and cocaine self-administration after oral administration". European Journal of Pharmacology. 553 (1–3): 149–56.
doi:
10.1016/j.ejphar.2006.09.024.
PMID17067572.
^Howell LL, Carroll FI, Votaw JR, Goodman MM, Kimmel HL (February 2007). "Effects of combined dopamine and serotonin transporter inhibitors on cocaine self-administration in rhesus monkeys". The Journal of Pharmacology and Experimental Therapeutics. 320 (2): 757–65.
doi:
10.1124/jpet.106.108324.
PMID17105829.
S2CID9205978.