Lobeline effects on tonic and methamphetamine-induced dopamine release

Biochem Pharmacol. 2008 Mar 15;75(6):1411-5. doi: 10.1016/j.bcp.2007.11.019. Epub 2007 Dec 4.

Abstract

The mechanisms of interaction between lobeline and the dopamine transporter (DAT) or the vesicular monoamine transporter (VMAT-2) are not clear. The goal of this study was to elucidate the effects of lobeline on these transporters in a cell system co-expressing the DAT and VMAT-2. Lobeline caused release of [(3)H]dopamine to a similar extent as reserpine (VMAT-2 inhibitor), but was less efficacious than methamphetamine or dopamine. Additionally, lobeline decreased the [(3)H]dopamine-releasing effects of methamphetamine, unlike reserpine which increased release by methamphetamine. These results suggest that lobeline has unique properties at the DAT and VMAT-2 which may make it useful as a pharmacotherapeutic to treat methamphetamine abuse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amphetamine-Related Disorders / drug therapy
  • Cell Line
  • Cocaine / analogs & derivatives
  • Cocaine / pharmacology
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Dopamine Agents / pharmacology*
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Dopamine Uptake Inhibitors / pharmacology
  • Humans
  • Lobeline / pharmacology*
  • Methamphetamine / pharmacology*
  • Nomifensine / pharmacology
  • Reserpine / pharmacology
  • Vesicular Monoamine Transport Proteins / antagonists & inhibitors
  • Vesicular Monoamine Transport Proteins / metabolism*

Substances

  • Dopamine Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • SLC18A2 protein, human
  • Vesicular Monoamine Transport Proteins
  • Nomifensine
  • Methamphetamine
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Reserpine
  • Lobeline
  • Cocaine
  • Dopamine