Lobelia inflata L. for

Sophora species [Leguminosae]) and the piperidine alkaloid lobeline (37) (from Lobelia inflata L. [Campanulaceae]), which have high affinity for 4p2 nAChRs lobeline also improves learning and is anxiolytic in vivo [137, 150, 151] (Scheme 42.9). Cytisine and derivatives may also be of therapeutic interest for PD (see Sect. 4). Huperzine A and tacrine hybrid structures (huprines) are also under investigation as nAChR agonists for AD, in addition to their documented ChE inhibitory and Mi mAChR agonistic properties [10] (see Sect. 2.2). 

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. 

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 ... 

L. inflata L. is a traditional medicinal plant native to North America. It contains several piperidine alkaloids. The main alkaloid is lobeline which has a stimulatory effect on the respiratory center and it is applied in the cases of asthma, gas- and narcotic-poisoning. Thus, lobeiine is currently the subject of renewed interest for the treatment of drug abuse and neurological disorders, like Alzheimer s or Parkinson s disease, which pose an important public health problem in industrial countries. As lobeiine can act as a competitive nicotinic receptor antagonist, it is frequently used in antismoking preparations. Interest in Lobelia alkaloids, and in particular (-)-lobeline, the most active of them, has increased in recent years due to their activity on the central nervous system (CNS). 

Lobelia was named after a Flemish botanist, Matthias L Obel (Robbers et al. 1996). Inflata refers to the hollow, distended fruit. It was also used by Native Americans as a substitute for tobacco. It was used medicinally by a group of physicians during the nineteenth century C.E. (Tyler 1994). However, due to toxicity and better treatments for tobacco dependence, lobelia is now rarely, if ever, indicated. Chemical Constituents... 

Samuel Thomson praised the use of L. inflata and L. syphilitica for an array of diseases, including rabies, measles, and smallpox, and even for removing pimples and warts. He Usts other herbs to be used with lobelia, such as capsicum, ginger, bayberry, and sage, as well as goldenseal and comfrey, and peach tree bark and myyrh. Peppermint and spearmint may be added, and catnip too. 

Numerous methods for the alkaloidal assay of lobelia and its galenical preparations have been published and two recent critical surveys, by a special committee of the Society of Public Analysts and by Caulkin, indicate that the process of Markwell is satisfactory. Processes for the isolation and separation of the Ararious alkaloids have been protected by patent. Balandin states that Lobelia sessUiflora contains less alkaloid than L. inflata but yields a high-quality lobeline. 

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