Novel N-1,2-dihydroxypropyl analogs of lobelane inhibit vesicular monoamine transporter-2 function and methamphetamine-evoked dopamine release.

ABSTRACT: Lobelane, a chemically defunctionalized saturated analog of lobeline, has increased selectivity for the vesicular monoamine transporter 2 (VMAT2) compared with the parent compound. Lobelane inhibits methamphetamine-evoked dopamine (DA) release and decreases methamphetamine self-administration. Unfortunately, tolerance develops to the ability of lobelane to decrease these behavioral effects of methamphetamine. Lobelane has low water solubility, which is problematic for drug development. The aim of the current study was to determine the pharmacological effect of replacement of the N-methyl moiety with a chiral N-1,2-dihydroxypropyl (N-1,2-diol) moiety, which enhances water solubility, altering the configuration of the N-1,2-diol moiety and incorporating phenyl ring substituents into the anal

SUBMITTER: Horton DB 

PROVIDER: S-EPMC3186287 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature