A novel and selective monoamine oxidase B substrate.
Cyclic five- and six-membered tertiary allylamines constitute a unique class of monoamine oxidase substrates that undergo a net two-electron alpha-carbon oxidation to form the cyclic, conjugated eniminium metabolites. The corresponding saturated pyrrolidinyl and piperidinyl systems are not substrates for this flavoenzyme system. In an attempt to evaluate possible contributions that pi-orbital stabilization of the putative alpha-carbon radical intermediates may play in the catalytic pathway, we have examined the substrate properties of 3-methyl-6-phenyl-3-aza-bicyclo[4.1.0]heptane, the 3,4-cyclopropyl analog of the selective monoamine oxidase B substrate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results, which document the first reported example of a saturated, cyclic tertiary amine with monoamine oxidase substrate properties, are consistent with alpha-carbon radical stabilization as a contributing factor in the catalytic pathway.
Department of Medicinal Chemistry and Laboratory for Applied Drug Design and Synthesis, The University of Mississippi, University, MS 38677, USA. jrimoldi@olemiss.edu
John M
JM
Rimoldi
Satish G
SG
Puppali
Emre
E
Isin
Philippe
P
Bissel
Ashraf
A
Khalil
Neal
N
Castagnoli
D000818:Animals; D002384:Catalysis; D008401:Gas Chromatography-Mass Spectrometry; D008995:Monoamine Oxidase / Q000378:metabolism*; D010215:Papio; D021241:Spectrometry, Mass, Electrospray Ionization; D013379:Substrate Specificity
D008995:Monoamine Oxidase