Vanoxerine

Definition

ChEBI: Vanoxerine is an N-alkylpiperazine that consists of piperazine bearing 2-bis(4-fluorophenyl)methoxy]ethyl and 3-phenylpropyl groups at positions 1 and 4 respectively. Potent, competitive inhibitor of dopamine uptake (Ki = 1 nM for inhibition of striatal dopamine uptake). Has > 100-fold lower affinity for the noradrenalin and 5-HT uptake carriers. Also a potent sigma ligand (IC50 = 48 nM). Centrally active following systemic administration. It has a role as a dopamine uptake inhibitor. It is a N-alkylpiperazine, an organofluorine compound, a tertiary amino compound and an ether. It is a conjugate base of a vanoxerine(2+).

Biological Activity

vanoxerine is an antagonist of dopamine transporter (dat1) with ki value of 16.9nm [1].as an antagonist of dat, vanoxerine is developed for treatment of parkinson's disease and depression but has no effect on these diseases. vanoxerine is also found to have desirable cardiac antiarrhythmic properties. it is a blocker of cardiac herg (hkv11.1) with ic50 value of 0.84nm. it also blocks the ica,l and hnav1.5 channel with ic50 values of 320nm and 830nm, respectively. vanoxerine does not significantly prolong purkinje fiber apd60 and apd90 and has no significant effect on qt or tdr. further, the

References

[1] giros b, el mestikawy s, godinot n, zheng k, han h, yang-feng t, caron mg. cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. mol pharmacol. 1992 sep;42(3):383-90.
[2] lacerda ae, kuryshev ya, yan gx, waldo al, brown am. vanoxerine: cellular mechanism of a new antiarrhythmic. j cardiovasc electrophysiol. 2010 mar;21(3):301-10.