Lobeline

Potential uses

Lobeline has been sold, in tablet form, for use as a smoking cessation aid, but scientific research has not provided supporting evidence for this use. Lobeline has also been studied for the treatment of other drug addictions such as addiction to amphetamines, cocaine, or alcohol; however, there is limited clinical evidence of any efficacy.

Toxicity

Ingestion of lobeline may cause nausea, vomiting, diarrhea, coughing, dizziness, visual disturbances, hearing disturbances, mental confusion, weakness, slowed heart rate, increased blood pressure, increased breathing rate, tremors, and seizures. Lobeline has a narrow therapeutic index: the potentially beneficial dose of lobeline is very close to the toxic dose.

Pharmacology

Lobeline has multiple mechanisms of action, acting as a VMAT2 ligand, which stimulates dopamine release to a moderate extent when administered alone, but reduces the dopamine release caused by methamphetamine. It also inhibits the reuptake of dopamine and serotonin, and acts as a mixed agonist–antagonist at nicotinic acetylcholine receptors to which it binds at the subunit interfaces of the extracellular domain. It is also an antagonist at μ-opioid receptors. It seems to be a P-glycoprotein inhibitor, according to at least one study. It has been hypothesized that P-glycoprotein inhibition reduces chemotherapeutic resistance in cancer, presumably affecting any substrates of P-gp.

Analogous compounds, such as lobelane (a minor alkaloid found in the same plants) and its synthetic derivatives have similar biological effects with somewhat different relative affinities to VMAT and other proteins. A related alkaloid sedamine, with only one 2-phenylethyl group on the piperidine ring and found in plants of genus sedum, is known to be an inhibitor of pea seedlings amine oxidase, but its affinity to proteins such as the dopamine transporter has apparently not been tested.

References

References

1. (February 2012). "Lobeline for smoking cessation". The Cochrane Database of Systematic Reviews.
2. (December 2003). "Smoking cessation". Respiratory Care.
3. (2008). "Novel pharmacological approaches for treating tobacco dependence and withdrawal: current status". Drugs.
4. (September 2007). "Lobelane decreases methamphetamine self-administration in rats". European Journal of Pharmacology.
5. (January 2005). "Lobeline attenuates methamphetamine-induced changes in vesicular monoamine transporter 2 immunoreactivity and monoamine depletions in the striatum". The Journal of Pharmacology and Experimental Therapeutics.
6. (August 2006). "Lobeline augments and inhibits cocaine-induced hyperactivity in rats". Life Sciences.
7. (June 2009). "Lobeline, a nicotinic partial agonist attenuates alcohol consumption and preference in male C57BL/6J mice". Physiology & Behavior.
8. "Lobelia". [[drugs.com]].
9. "Lobelia". drugs.com.
10. "Symptoms of Plant poisoning -- Lobeline".
11. (November 2006). "Vesicular monoamine transporter 2: role as a novel target for drug development". The AAPS Journal.
12. (April 2007). "Computational neural network analysis of the affinity of lobeline and tetrabenazine analogs for the vesicular monoamine transporter-2". Bioorganic & Medicinal Chemistry.
13. (August 2005). "Defunctionalized lobeline analogues: structure-activity of novel ligands for the vesicular monoamine transporter". Journal of Medicinal Chemistry.
14. (March 2008). "Lobeline effects on tonic and methamphetamine-induced dopamine release". Biochemical Pharmacology.
15. (September 2004). "Effects of methamphetamine and lobeline on vesicular monoamine and dopamine transporter-mediated dopamine release in a cotransfected model system". The Journal of Pharmacology and Experimental Therapeutics.
16. (October 2006). "Des-keto lobeline analogs with increased potency and selectivity at dopamine and serotonin transporters". Bioorganic & Medicinal Chemistry Letters.
17. (July 1997). "Pharmacology of lobeline, a nicotinic receptor ligand". The Journal of Pharmacology and Experimental Therapeutics.
18. (January 2003). "Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats". Pharmacology, Biochemistry, and Behavior.
19. (October 2005). "Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations". The EMBO Journal.
20. (July 2007). "Lobeline, a potential pharmacotherapy for drug addiction, binds to mu opioid receptors and diminishes the effects of opioid receptor agonists". Drug and Alcohol Dependence.
21. (September 2008). "Lobeline, a piperidine alkaloid from Lobelia can reverse P-gp dependent multidrug resistance in tumor cells". Phytomedicine.
22. (January 2015). "P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review". Journal of Advanced Research.
23. (September 2004). "Lobeline analogs with enhanced affinity and selectivity for plasmalemma and vesicular monoamine transporters". The Journal of Pharmacology and Experimental Therapeutics.
24. "(-)-Sedamine, CID=442657". National Center for Biotechnology Information.
25. (October 2001). "Probing the active site of pea seedlings amine oxidase with optical antipodes of sedamine alkaloids". Journal of Enzyme Inhibition.