Lobeline is a pyridine
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
found in a variety of plants, particularly those in the genus ''
Lobelia
''Lobelia'' () is a genus of flowering plants comprising 415 species, with a subcosmopolitan distribution primarily in tropical to warm temperate regions of the world, a few species extending into cooler temperate regions.Huxley, A., ed. (1992 ...
'', including Indian tobacco (''
Lobelia inflata
''Lobelia inflata'', also known as Indian tobacco or puke weed, is a species of ''Lobelia'' native to eastern North America, from southeastern Canada (Nova Scotia to southeast Ontario) south through the eastern United States to Alabama and west ...
''), Devil's tobacco (''
Lobelia tupa
''Lobelia tupa'' is a species of ''Lobelia'' native to central Chile from Valparaíso south to Los Lagos regions.Flora Chilena''Lobelia tupa''/ref>
Lobelia tupa is an evergreen perennial plant which grows up to 4 m tall and thrives in dry soils ...
''), great lobelia (''
Lobelia siphilitica
''Lobelia siphilitica'', the great blue lobelia, great lobelia, or blue cardinal flower, is a plant species within the family Campanulaceae. It is an herbaceous perennial dicot native to eastern and central Canada and United States. There are t ...
''), ''
Lobelia chinensis
''Lobelia chinensis'', commonly known as Asian lobelia, Chinese Lobelia, and Herba Lobellae Chinensis, is a species of flowering plant in the family Campanulaceae. It is one of the 50 fundamental herbs used in traditional Chinese medicine, where ...
'', and ''
Hippobroma longiflora''. In its pure form, it is a white amorphous powder which is freely soluble in water.
Potential uses
Lobeline has been sold, in tablet form, for use as a
smoking cessation
Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often m ...
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 therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...
; the potentially beneficial dose of lobeline is very close to the toxic dose.
Pharmacology
Lobeline has multiple mechanisms of action, acting as a VMAT2
The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...
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
Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the Synapse, pre-synaptic neuron at a synapse) or glial cell after it has performed its function of ...
of dopamine and serotonin, and acts as a mixed agonist–antagonist at nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
s 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
Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless liquid with an odor de ...
ring and found in plants of genus sedum
''Sedum'' is a large genus of flowering plants in the family Crassulaceae, members of which are commonly known as stonecrops. The genus has been described as containing up to 600 species, subsequently reduced to 400–500. They are leaf succul ...
, 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.
See also
* Lobelanine
Lobelanine is a chemical precursor in the biosynthesis of lobeline
Lobeline is a pyridine alkaloid found in a variety of plants, particularly those in the genus ''Lobelia'', including Indian tobacco ('' Lobelia inflata''), Devil's tobacco ('' L ...
* Lobelanidine
Lobelanidine is a chemical analog of lobeline
Lobeline is a pyridine alkaloid found in a variety of plants, particularly those in the genus ''Lobelia'', including Indian tobacco ('' Lobelia inflata''), Devil's tobacco ('' Lobelia tupa''), great ...
References
{{Opioid receptor modulators
Antidepressants
Nicotinic agonists
Ketones
Mu-opioid receptor antagonists
VMAT inhibitors
Piperidine alkaloids
Secondary alcohols
Plant toxins