Lobelia inflata Lobeline

Lobelia cathechu guvacoline guvacine Lobelia inflata Lobeline Nicotinic ACh agonist... 

Biological activities biosynthesis of piperidine alkaloids HPLC and LC-MS/MS Lobelia inflata lobeline and their derivates pelletierine Piper nigrum piperine Punic a granatum... 

Lobelia Lobelia inflata Lobeline Smoke or tea as marihuana substitute Mild euphoriant... 

Other mechanisms, such as the inhibition of -amyloid formation. There are several other alkaloids which are nicotinic agonists at the cholinergic receptor such as lobeline (89) from Lobelia inflata. Lobelia inflata a could be exploited to influence cholinergic function in AD. Sophoramine (90) and cytisine (91), found in members of the Leguminosae, have nicotinic actions but they do not appear to have been developed for any pharmaceutical purposes, probably because of their toxicity. 

Alkaloids with the piperidine nucleus, such as pelletierine (Punica grana-tum), lobelanine Lobelia inflata) and piperine Piper nigrum), have a typical biosynthesis pathway. It starts with L-lysine and continues via cadaverine (biogenic amine), A -piperideine and A -piperidinium cations and lobelanine, to be synthesized as lobeline. Piperine is synthesized from A -piperideine via piperidine (Figure 49). For the transformation from A -piperideine to A -piperideine cation, the residue from acetyl-CoA is needed, together with SAM activity in the transformation to lobelanine. Piperine is synthesized from piperidine through the formation of amide. 

N.A. Lobelia inflata L. Lobeline, lobelidiol, lobelanidine, carboxylic acid.99-100-289 Respiratory stimulant, antispasmodic, induce vomiting. 

Lobelia or Indian tobacco consists of the dried leaves and tops of Lobelia inflata (Campanulaceae), an annual herb from the USA and Canada. Lobelia contains about 0.2-0.4% of alkaloids, of which the piperidine derivative lobeline (Figure 6.23) is the chief constituent. Minor alkaloids identified include closely related structures, e.g. lobelanine (Figure 6.23). The North American Indians employed lobelia as an alternative or substitute for tobacco (Nicotiana tabacum Solanaceae), and it is found that lobeline stimulates nicotinic receptor sites in a similar way to nicotine, but with a weaker effect. Lobeline has been employed in preparations intended as smoking deterrents. The crude plant drug has also long been used to relieve asthma and bronchitis, though in large doses it can be quite toxic. 

Lobeline 126, a 2,6-disubstituted /V-mcthy I piperidine, is used as a respiratory stimulant and is also found in the leaves and seeds of Lobelia inflata L. Lobeliaceae (or Indian tobacco) . 

Nicotiana tabacum, and lobeline, present in the dried leaves and tops of the herb, Lobelia inflata (13). Both nicotine and lobeline act as agonists on a specific type of acetylcholine receptor, the nicotinic cholinergic receptor. In mammals, nicotinic cholinergic receptors mediate cholinergic neurotransmission in skeletal muscles, autonomic ganglia, and the central nervous system. At these sites nicotine s action has two phases, excitation and depression. Insect central nervous tissues are rich in nicotinic cholinergic receptors (cf. 14), but their role in behavior is not well understood. 

Today, Lobelia inflata (Indian tobacco) or its derivatives (lobeline hydrochloride and lobeline sulfate) are used for much the same purpose and are marketed throughout Europe in a number of multi-ingredient preparations 73 Similarly, Poly gala senega (Seneca snakeroot), listed in the supply table as an expectorant, is widely marketed throughout Europe and South Africa for respiratory-tract complaints 7 A popularly prescribed diuretic on the supply table was Juniperus communis (juniper) it is still widely manufactured and dispensed for the same purpose today75... 

Lobelia inflata (Indian tobacco) contains lobeline and other pyridine alkaloids. It has been used as an emetic, antidepressant, respiratory stimulant, an aid to smoking cessation, and a treatment for metamfetamine abuse (1). 

Lobeline is derived from the plant Lobelia inflata (Indian tobacco). It is both an agonist and an antagonist at nicotinic receptors, although it is not structurally related to nicotine (1). It inhibits nicotine- and amphetamine-induced dopamine release by interacting with the tetra-benazine-binding site on the monoamine transporter. It also inhibits dopamine re-uptake. It has been used in smoking cessation, but is ineffective (2). 

Lobeline (92), an alkaloid obtained from Lobelia inflata binds with high affinity at some nicotinic receptors, and it produces some (but not all) of the effects of (-)-nicotine(134). 

The discovery of morphine by Serturner (1809—1817) stimulated an enormous activity in the field of plant products and most alkaloids still used today were found during the first half of the last century. The years to follow were not so productive, ephedrine being isolated in 1887 and scopolamine in 1888, and of all the alkaloids found in the first half of the 20th century, only the ergot alkaloids and (to some limited extent) lobeline from Lobelia inflata (Campan.) have found use in human therapy. 

Hairy root cultures of Lobelia inflata, induced by Agrobacterium rhizogenes, were found to produce lobeline in levels comparable to those found in the cultivated plant [534]. Different clones responded quite differently to illumination with regard to the levels of lobeline produced in their hairy root cultures [535]. 

Isolates from Indian tobacco (Lobelia inflata L.), as a crude mixture of bases, have been recognized as expectorants. The same (or similar) fractions were also used both in the treatment of asthma and as emetics. The principal alkaloid in L. inflata is lobeline (49), an optically active tertiary amine which, unusual among alkaloids, is reported to readily undergo mutarotation, a process normally associated with sugars. Interestingly, it appears that the aryl-bearing side chains in (49) are derived from phenylalanine (25, R = H) (40). 

The alkaloid lobeline (as derived from Lobelia inflata) bears a striking resem-blanee to nieotine, and both have similar chemical actions. This may extend to cancer treatment. Heinerman observes that the nineteenth century American herbalist... 

Lobeline, the chief alkaloid of Lobelia inflata and other Lobelia spp. has a nicotinelike action and has had limited use as a respiratory stimulant... 

Lobeline.—The results of feeding experiments with DL-[2- C]lysine and dl-[2- Clphenylalanine in Lobelia inflata have shown that these amino-acids are both specific precursors for the alkaloid lobeline (13). In further experiments, DL-[3- C]phenylalanine, [3- C]cinnamic acid, and [3- C]-3-hydroxy-3-phenylpropionic acid [as (9)] have been found to be specific precursors for lobeline (13). These results are consistent with the anticipated pathway " to lobeline illustrated in Scheme 2, with benzoylacetic acid (10) as the intermediate which couples with A -piperideine to give the intermediate (11). The probability of 3-hydroxy-3-phenylpropionic acid (9) being an intermediate in lobeline biosynthesis is increased by the isolation of this acid from L. inflata ... 

Lobelia tupa Known in Chile as tupa or tabaco deldiablo, Mapuche Indians have been reported to smoke the leaves of this plant as an inebriant (Duke 1985 Schultes Hofmann 1980). Piperidine alkaloids not known to be psychoactive are found in this plant, although lobeline is said to exert a nicotine-like activity. Lobelia inflata was used ceremonially by North American Crow Indians, and in love magic by Mesquakie and Pawnee Indians (IGndscher 1992). 

Piperidine alkaloids occur in only a few species of higher plants. However, (S)-pipecolic acid 3 [121] is widely distributed in higher plants, microorganisms and animals. Lobeline 4 is the main constituent of lobelia alkaloids (Lobelia inflata, Campanulaceae). It is a respiratory stimulant in mammals. Pi-perine 5 is the active ingredient in black pepper (Piper nigrum). On hydrolysis it furnishes piperic acid 6 and piperidine (hence its name) [122] ... 

Lobeline is the principal lobelia alkaloid. It occurs in the seeds and herb of Indian tobacco (Lobelia inflata and Lobeliaceae). It is used as a respiratory stimulant. Its sulfate salt is used in antismoking tablets. 

Another series of lysine derived alkaloids occurs in the genus Lobelia (Campanulaceae). One of these compounds, lobeline (39) (Fig. 29.13) (from Lobelia inflata, Indian tobacco), has been used in antismoking preparations. Both lobeline and nicotine are classed as ganglionic stimulants. Therapeutically, lobeline is hardly used today (Fodor and Colosanti, 1985). Poisoning of cattle because of ingestion of Lobelia berlandieri has occurred in Texas and Mexico... 

Lobelin (-)-lobelin, cfr-8,10-diphenyl-lobelionol, the main Lobelia alkaloid (see). Structurally, it is a lo-belionol, in which both Rj and R2 are phenyl (-C H ) groups. L. crystallizes as colorless needles, m.p. 130-131 °C, [o]d-43° (c = 1, ethanol). It is isolated from Lobelia inflata, and is used medicinally as a respiratory analeptic. On account of its nicotine-like properties, it is also used in the treatment of smoking addiction. Simultaneous administration of nicotine and L. has an additive effect, leading to nausea and aversion. 

Lobeline is found in Lobelia inflata along with lobelanine and lobelanidine. The main ring in lobeline is derived from lysine via piperidine, while the two benzene rings it contains derive from phenylalanine via the shikimic acid pathway (Samuelsson 1992). 

While for developing of simple piperidine alkaloids, e.g., pelletierine (Punica granatum), piperine (Piper nigrum et longum), and lobeline (Lobelia inflata), only one molecule of lysine is necessary, for quinolizidine alkaloids - e.g., lupinine (Lupinus luteus), sparteine of antiarrhythmic activity (Sarothamnus scoparius), and cytisine of respiratory stimulant effect (Laburnum species) - two molecules of lysines are indispensable. It was also proved that lycopodine (Lycopodium tristachyum, clubmoss) of quinolizidine structure has no polyketide origin, but it is a modified dimer of pelletierine, which, in turn, is derivable from lysine and acetate. 

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