N,O-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate

N,O-Dimethyl-4β-(2-naphthyl)piperidine-3β-carboxylate (DMNPC) is a piperidine based stimulant drug which is synthesised from arecoline. It is similar to nocaine in chemical structure, and has two and a half times more activity than cocaine as a dopamine reuptake inhibitor. However it is also a potent serotonin reuptake inhibitor, with similar affinity to fluoxetine.



The stereochemistry of DMNPC dramatically affects it's binding affinity with the SS enantiomer having the highest overall activity. The 3R,4S enantiomer demonstrates the highest selectivity for 5-HTT.

In animal studies, DMNPC exhibits similar potency as fluoxetine but with greater activity for DAT and NET. N-Demethylation of DMNPC has shown to produce a 3-fold increase in potency for 5-HTT.

Synthesis
A racemic mixture of DMNPC can be synthesized from freebase arecoline in a grignard reaction with 2-naphthylmagnesium bromide. Further reactions and separation methods can be used to produce enantiomerically pure products.

A substantially simpler method that ablates the carbomethoxy ester substituent has been demonstrated by D. Koch in Ex2: