Abstract
Lobeline diminishes the behavioral and neurochemical effects of nicotine and amphetamines, and is considered a potential pharmacotherapy for drug abuse and addiction. Lobeline has high affinity for nicotinic acetylcholine receptors and inhibits the function of vesicular monoamine and dopamine transporters. The present study investigated the less-explored interaction of lobeline and the endogenous opioid system. In guinea pig brain homogenates, lobeline displaced ( K i = 0.74 μM) the binding of [ 3H]DAMGO [(D-Ala 2, N-ME-Phe 4, Gly 5-ol)-enkephalin]. In a functional assay system comprised of MOR-1 μ opioid receptors and GIRK2 potassium channels expressed in Xenopus oocytes, lobeline had no effect on the resting current, but maximally inhibited (IC 50 = 1.1 μM) morphine- and DAMGO-activated potassium current in a concentration-dependent manner. In a second functional assay, lobeline-evoked [ 3H]overflow from rat striatal slices preloaded with [ 3H]dopamine was not blocked by naltrexone. Importantly, concentrations of lobeline (0.1–0.3 μM) that did not have intrinsic activity attenuated (∼50%) morphine-evoked [ 3H]overflow. Overall, the results suggest that lobeline functions as a μ opioid receptor antagonist. The ability of lobeline to block psychostimulant effects may be mediated by opioid receptor antagonism, and lobeline could be investigated as a treatment for opiate addiction.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
