Clinical data
ATC code
  • none
Legal status
Legal status
  • (+)-(E)-1-[(1R,2R,3S)-3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbaldehyde O-methyloxime
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PubChem CID
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Chemical and physical data
Molar mass327.25 g·mol−1
3D model (JSmol)
  • Clc1ccc(cc1Cl)[C@H]3C[C@H]2N(C)[C@H](CC2)[C@@H]3\C=N\OC
  • InChI=1S/C16H20Cl2N2O/c1-20-11-4-6-16(20)13(9-19-21-2)12(8-11)10-3-5-14(17)15(18)7-10/h3,5,7,9,11-13,16H,4,6,8H2,1-2H3/b19-9+/t11-,12+,13+,16+/m0/s1 checkY
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Brasofensine (NS-2214, BMS-204756) is a phenyltropane dopamine reuptake inhibitor that had been under development by Bristol-Myers Squibb and defunct company NeuroSearch for the treatment of Parkinson's and Alzheimer's diseases.


In 1996, brasofensine entered phase I trials in the United States and phase II trials in Denmark.[1] From 1996 to 1999, Bristol-Myers Squibb (BMS) was involved in development and testing before exiting the collaboration with NeuroSearch. In 2001, its development was confirmed to be discontinued.[2]


In animal models of Parkinson's disease, brasofensine was effective in stimulating locomotor activity and reversing akinesia.[3] Phase II trials in humans were conducted in 1996 and brasofensine was shown to be both effective and well tolerated at a dose of 4 mg;[4] however, development was stopped after in vivo cis-anti isomerization of the 2α-methyloxime group was reported.[5]

In Parkison's disease, symptoms do not begin to manifest until there has been an 80% reduction in dopaminergic neurons, particularly in the substantia nigra brain region.

Metabolism and distribution

Brasofensine is not particularly stable and is readily metabolized. It was studied in humans in doses ranging from 2-50 mg.[6] Because metabolism in rats is much greater than in humans, the amount of metabolites detected in their urine (and feces) was also much greater than for humans, who excrete more of the product intact. In radiolabeling studies using 14C, most (~90%) of the 14C was detected in the urine of humans, whereas for rats as much as 80% of the 14C was in their feces.[6]

The isomerization of brasofensine did not involve epimerization at 2-position of the tropane ring, but rather involved the E/Z-isomerization of the imine (i.e. "methyl-aldoxime").[6] It was believed that this process occurs in vivo, although it cannot be ruled out as a possibility that some isomerization also occurs prior to ingestion. The (Z)-isomer has been assigned the name BMS-205912.

Imine formation is a reversible process, and in the study by Zhu et al.,[6] none of the aldehyde was recovered/detected by GC-MS. Instead, the breakdown products were N-demethylated metabolites.


  1. ^ Yu P (December 2000). "Brasofensine NeuroSearch". Current Opinion in Investigational Drugs. 1 (4): 504–507. PMID 11249705.
  2. ^ "Brasofensine". DrugBank. 2007. Retrieved 16 March 2023.
  3. ^ Pearce RK, Smith LA, Jackson MJ, Banerji T, Scheel-Krüger J, Jenner P (September 2002). "The monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP-treated and levodopa-primed common marmosets". Movement Disorders. 17 (5): 877–886. doi:10.1002/mds.10238. PMID 12360536. S2CID 46483126.
  4. ^ Frackiewicz EJ, Jhee SS, Shiovitz TM, Webster J, Topham C, Dockens RC, et al. (February 2002). "Brasofensine treatment for Parkinson's disease in combination with levodopa/carbidopa". The Annals of Pharmacotherapy. 36 (2): 225–230. doi:10.1345/aph.1A152. PMID 11847938. S2CID 21429193.
  5. ^ Runyon SP, Carroll FI (2006). "Dopamine transporter ligands: recent developments and therapeutic potential". Current Topics in Medicinal Chemistry. 6 (17): 1825–1843. doi:10.2174/156802606778249775. PMID 17017960.
  6. ^ a b c d Zhu M, Whigan DB, Chang SY, Dockens RC (January 2008). "Disposition and metabolism of [14C]brasofensine in rats, monkeys, and humans". Drug Metabolism and Disposition. 36 (1): 24–35. doi:10.1124/dmd.107.016139. PMID 17908924. S2CID 2387909.