(-)-2β-(1,2,4-Oxadiazol-5-methyl)-3β-phenyltropane

(-)-2β-(1,2,4-Oxadiazol-5-methyl)-3β-phenyltropane
Systematic (IUPAC) name
(1R,2S,3S,5S)-8-methyl-2-(1,2,4-oxadiazol-5-methyl)-3-phenyl-8-azabicyclo[3.2.1]octane
Clinical data
Pregnancy cat.  ?
Legal status  ?
Identifiers
ATC code  ?
Chemical data
Formula C17H21N3O 
Mol. mass 283.367
SMILES eMolecules & PubChem

RTI-126, ((-)-2β-(1,2,4-oxadiazol-5-methyl)-3β-phenyltropane) is a phenyltropane derivative which acts as a potent monoamine reuptake inhibitor and stimulant drug. It is around 5x more potent a stimulant than cocaine, but is relatively unselective, binding to all three monoamine transporters although still with some selectivity for the dopamine transporter.[1] RTI-126 has a fast onset of effects and short duration of action, and its pharmacological profile in animals is among the closest to cocaine itself out of all the drugs in the RTI series. Its main application in scientific research has been in studies investigating the influence of pharmacokinetics on the abuse potential of stimulant drugs, with its rapid entry into the brain thought to be a key factor in producing its high propensity for development of dependence in animals.[2][3]

RTI-126 is not explicitly illegal anywhere in the world; its similar pharmacological activity to cocaine makes it possible that it could be considered a controlled substance analogue in countries such as the USA, Australia and New Zealand which have controlled substance analogue legislation, but the replacement of the 2β-carbomethoxy group with methyloxadiazole is a significant structural alteration and it is unclear whether it could be considered "substantially similar" in chemical structure so as to bring it within the definition of a controlled substance analogue. There is as yet no case law defining what constitutes a substantially similar chemical structure, and so it is not possible to say for certain whether RTI-126 would be an illegal drug or not.

It is interesting to note that the structurally related compound (-)-2β-(3-methyl-5-isoxazolyl)nortropane is a potent and selective agonist for nicotinic acetylcholine receptors, with twice the potency of nicotine.[4]


See also

References

  1. ^ Carroll, FI; Gray, JL; Abraham, P; Kuzemko, MA; Lewin, AH; Boja, JW; Kuhar, MJ (1993). "3-Aryl-2-(3'-substituted-1',2',4'-oxadiazol-5'-yl)tropane analogues of cocaine: affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters". Journal of medicinal chemistry 36 (20): 2886–90. doi:10.1021/jm00072a007. PMID 8411004. 
  2. ^ Kimmel, HL; Carroll, FI; Kuhar, MJ (2001). "Locomotor stimulant effects of novel phenyltropanes in the mouse". Drug and alcohol dependence 65 (1): 25–36. doi:10.1016/S0376-8716(01)00144-2. PMID 11714587. 
  3. ^ Kimmel, HL; O'Connor, JA; Carroll, FI; Howell, LL (2007). "Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys". Pharmacology, biochemistry, and behavior 86 (1): 45–54. doi:10.1016/j.pbb.2006.12.006. PMC 1850383. PMID 17258302. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1850383. 
  4. ^ Cheng J, Izenwasser S, Zhang C, Zhang S, Wade D, Trudell ML. Synthesis and nicotinic acetylcholine receptor binding affinities of 2- and 3-isoxazolyl-8-azabicyclo[3.2.1]octanes. Bioorganic and Medicinal Chemistry Letters. April 2004; 14(7):1775-1778. doi:10.1016/j.bmcl.2004.01.025 PMID 15026069