(-)-2β-(3-(4-methylphenyl)isoxazol-5-yl)-3β-(4-chlorophenyl)tropane

Drugbox
IUPAC_name = (1R,2S,3S,5S)-8-methyl-2-(3-(4-methylphenyl)isoxazol-5-yl)-3-(4-chlorophenyl)-8-azabicyclo [3.2.1] octane

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PubChem= 9800708
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C=24 | H=25 | Cl=1 | N=2 | O=1
molecular_weight = 392.920
smiles = CC1=CC=C(C=C1)C2=NOC(=C2) [C@@H] 3 [C@H] 4CC [C@H] (N4C)C [C@@H] 3C5=CC=C(C=C5)Cl
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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, [Carroll FI, Pawlush N, Kuhar MJ, Pollard GT, Howard JL. 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". 2004 Jan 15;47(2):296-302. PMID 14711303] however it produces relatively mild stimulant effects, with a slow onset and long duration of action. [Carroll FI, Fox BS, Kuhar MJ, Howard JL, Pollard GT, Schenk S. Effects of dopamine transporter selective 3-phenyltropane analogs on locomotor activity, drug discrimination, and cocaine self-administration after oral administration. "European Journal of Pharmacology". 2006 Dec 28;553(1-3):149-56. PMID 17067572] 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. [Carroll FI, Howard JL, Howell LL, Fox BS, Kuhar MJ. Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse. AAPS Journal". 2006 Mar 24;8(1):E196-203. PMID 16584128] [Sofuoglu M, Kosten TR. Emerging pharmacological strategies in the fight against cocaine addiction. "Expert Opinion on Emerging Drugs". 2006 Mar;11(1):91-98. doi:10.1517/14728214.11.1.91] RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration, [Kimmel HL, O'Connor JA, Carroll FI, Howell LL. Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys. "Pharmacology, Biochemistry and Behaviour". 2007 Jan;86(1):45-54. PMID 17258302] [Kimmel HL, Negus SS, Wilcox KM, Ewing SB, Stehouwer J, Goodman MM, Votaw JR, Mello NK, Carroll FI, Howell LL. Relationship between rate of drug uptake in brain and behavioral pharmacology of monoamine transporter inhibitors in rhesus monkeys. "Pharmacology, Biochemistry and Behaviour". 2008 Sep;90(3):453-62. PMID 18468667] and significantly reduces rates of cocaine use, especially when combined with SSRIs, [Howell LL, Carroll FI, Votaw JR, Goodman MM, Kimmel HL. Effects of combined dopamine and serotonin transporter inhibitors on cocaine self-administration in rhesus monkeys. "Journal of Pharmacology and Experimental Therapeutics". 2007 Feb;320(2):757-65. PMID 17105829] and research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.

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