Difluoropine

Difluoropine (O-620) is a stimulant drug synthesised from tropinone, which acts as a potent and selective dopamine reuptake inhibitor. Difluoropine is unique among the tropane-derived dopamine reuptake inhibitors in that the active stereoisomer is the (S) enantiomer rather than the (R) enantiomer, the opposite way round compared to natural cocaine.^[1] It is structurally related to benztropine and has similar anticholinergic and antihistamine effects in addition to its dopamine reuptake inhibitory action.^[2]

Difluoropine

Clinical data
Other names	(S)-(+)-2β-Carbomethoxy-3α-(bis(4-fluorophenyl)methoxy)tropane
ATC code	none
Identifiers
IUPAC name methyl (1S,2S,3S,5R)-3-[bis(4-fluorophenyl)methoxy]-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
CAS Number	156774-35-5 Y
PubChem CID	190851
ChemSpider	165751
UNII	NA9FDN6R4M
ChEMBL	ChEMBL1945126
CompTox Dashboard (EPA)	DTXSID20935527
Chemical and physical data
Formula	C23H25F2NO3
Molar mass	401.454 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN1[C@@H]2CC[C@H]1[C@@H]([C@H](C2)OC(C3=CC=C(C=C3)F)C4=CC=C(C=C4)F)C(=O)OC
InChI InChI=1S/C23H25F2NO3/c1-26-18-11-12-19(26)21(23(27)28-2)20(13-18)29-22(14-3-7-16(24)8-4-14)15-5-9-17(25)10-6-15/h3-10,18-22H,11-13H2,1-2H3/t18-,19+,20+,21+/m1/s1 Key:XSYGBVSQKPLETJ-ANULTFPQSA-N
(verify)

Difluoropine has some stimulant effects in animals, although it is significantly less powerful than many of the potent phenyltropane derived stimulant drugs such as WIN 35,428 and RTI-55.^[3] It showed promising effects in alleviating the symptoms of Parkinson's disease in an animal model of the disorder.^[4]

It is not explicitly illegal anywhere in the world as of 2008^[update], but might be considered to be a controlled substance analogue of cocaine on the grounds of its related chemical structure, in some jurisdictions such as the United States, Canada, Australia and New Zealand.

See also

• List of cocaine analogues

References

1. Meltzer PC, Liang AY, Madras BK (June 1994). "The discovery of an unusually selective and novel cocaine analog: difluoropine. Synthesis and inhibition of binding at cocaine recognition sites". Journal of Medicinal Chemistry. 37 (13): 2001–10. doi:10.1021/jm00039a014. PMID 8027983.
2. Campbell VC, Kopajtic TA, Newman AH, Katz JL (November 2005). "Assessment of the influence of histaminergic actions on cocaine-like effects of 3alpha-diphenylmethoxytropane analogs". The Journal of Pharmacology and Experimental Therapeutics. 315 (2): 631–40. doi:10.1124/jpet.105.090829. PMID 16055673. S2CID 40671768.
3. Katz JL, Izenwasser S, Kline RH, Allen AC, Newman AH (January 1999). "Novel 3alpha-diphenylmethoxytropane analogs: selective dopamine uptake inhibitors with behavioral effects distinct from those of cocaine". The Journal of Pharmacology and Experimental Therapeutics. 288 (1): 302–15. PMID 9862785.
4. Madras BK, Fahey MA, Goulet M, Lin Z, Bendor J, Goodrich C, et al. (November 2006). "Dopamine transporter (DAT) inhibitors alleviate specific parkinsonian deficits in monkeys: association with DAT occupancy in vivo". The Journal of Pharmacology and Experimental Therapeutics. 319 (2): 570–85. doi:10.1124/jpet.106.105312. PMID 16885433. S2CID 7523758.