1-Lobeline

Synonyms 2-(3-pyridyl)piperidine 3-(2-pi-peridyl)pyridine neonicotine 

Anabasine occnrs in the tobacco species Nicotiana glauca, Anabasis aphylla L., Chenopodiaceae, and Solanaceae. It is nsed as an insecticide and as a metal anticorrosive agent. 

Colorless liquid boils at 271°C (519.8°F) freezes at 9°C (48.2°F) soluble in water and most organic solvents. 

The acute toxic symptoms include increased salivation, confusion, disturbed vision, photophobia, nausea, vomiting, diarrhea, respiratory distress, and convulsions. It causes respiratory muscle stimulation similar to that caused by lobeline. An oral lethal dose in dogs is 50 mg/kg. A subcutaneous lethal dose in guinea pigs is 10 mg/kg. 

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Isolates from Indian tobacco Q obelia inflata L.), as a cmde 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 T. 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). 

Billing 7 has provided a scheme for distinguishing between the hemlock bases and other alkaloids, such as sparteine, nicotine and lobeline. 

The presence of alkaloids in Lobelia injlata, Linn., was first recorded by Proctor. Lobeline was prepared by Lewis as a basic oil from which Siebert made and analysed a series of salts and proposed the formula, CigHjsOjN. In 1921 Bohringer and Sohne protected a process for the isolation and separation of three alkaloids, a-, 3 and y-lobelines. In the same year Wieland published the first of a series of papers in which is described the isolation of several groups of alkaloids, to most of which constitutional formulae have been assigned and, in some cases, confirmed... 

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 various alkaloids have been protected by patent. Balandin states that Lobelia sessiliflora contains less alkaloid than L. injiata but yields a high-quality lobeline. 

The carbonyl groups in the diketo- and keto-aleohol bases are not readily detected by the usual reagents and as these bases can be reduced to the dihydrie alcohols, it was assumed at first that lobeline and lobelanine contained one and two ether linkages respectively and formulse based on this assumption, and satisfying the other experimental evidence then available, were put forward by Wieland, Schopf and Hermsen, of which that for lobeline (II) may be quoted as an example. 

LOBELINE GROUP. The inter-relationships of the five members of this group have been given in Table A by reference to the general Formula I. The chief data on which this formula is based are as follows — ... 

All five alkaloids must have the same nuclear structure since lobeline is convertible into lobelanidine by hydrogenation and into lobelanine by oxidation, and worlobelanidine and worlobelanine yield lobelanidine and lobelanine respectively on A-methylation. 

Syntheses of members of the lobeline group have been effected by Wieland and Drishaus and by Seheuing and Winterhalder. JiorLobelane was prepared by the former authors by condensing 2 6-dimethylpyridine with benzaldehyde to 2 6-distyrylpyridine (IX), which was then reduced by sodium in alcohol, giving a mixture of meso-and trans- forms of 2 6-di-(3-phenylethylpiperidine (worlobelane). From this by crystallisation of the mixed hydrochlorides, meso-norlobelane was separated, which on A-methylation yielded lobelane (X) as the methiodide. 

The principal characteristics of the naturally occurring members of the lobeline group (see also Table A, p. 23) are as follows —... 

Z-Lobeline, C22H2,OoN, separates from alcohol, ether or benzene in glistening needles, m.p. 130-1°, — 42-85° (EtOH), readily soluble in... 

LELOBINE AND LOBININE GROUPS. These include the minor alkaloids of lobelia isolated from factory residues accumulated during the manufacture of lobeline. Their isolation and separation involve complicated processes of fractionation for which the original paper should be consulted. Their inter-relationships (Table A, p. 23 and general formula, I, p. 24) are similar to those among members of the lobeline group, but the effect of the presence of three or more asymmetric carbon atoms is more evident, thus there are already known six forms of the basic dihydric alcohol, lelobaiiidine. 

The methods of investigation used are the same in principle as those used successfully with the diketo-base, lobelanine (p. 24) in the lobeline series. 

Exhaustive Methylation. As in the lobeline group it is the diketo-bases, lelobanines (p. 30) in the lelobine series and lobinanines (p. 31) in the lobinine group, which give methiodides amenable to this mode of degradation. They are decomposed by alkali yielding an unsaturated neutral oil, which is hydrogenated and then, if necessary, oxidised to the saturated open chain diketone, e.g., see under lelobanine. 

Isotoma longiflora. This Peruvian plant contains an alkaloid, m.p. 190°, forming a hydrochloride, m.p. 160°. Pharmacological results are recorded and it is suggested that the alkaloid resembles lobeline of which it may be a derivative (Sanchez, Rev. Med. expU, (Peru), 1945, 4, 284 Chem. Abstr., 1948, 42, 1350). 

The alkaloid sedamine has been prepared under physiological conditions too (318). Aldolization of the immonium salt 200, obtained by mercuric acetate dehydrogenation of (2S,8R)-(—)-sedamine (199), with benzoylacetic acid produces (2S,6R,8S)-(—)-8,10-diphenyllobelinol (i.e., (—)-lobeline) (201). This determines its absolute configuration (319, 320). 

Likewise, a cis-2,6-disubstituted piperidine natural product, (-)-lobeline (98, Scheme 8.4.30) was synthesized from the chiral Af-alkyl pyridinium salt ent-80 via a sequence that included addition of a Reformatsky reagent to an intermediate oxazolidine. °... 

Lobeline Lobelia inf lata, -(also non-specific actions)... 

Lobeline. The alkaloid lobehne, whose mechanism of action in unclear but that appears to have dopamine reuptake blockade and nicotinic receptor antagonist properties (Dwoskin and Crooks 2002), was evaluated in a double-bhnd, randomized, placebo-controUed, multicenter trial involving 180 ciga-... 

Dwoskin LP, Crooks PA A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse. Biochem Pharmacol 63 89-98, 2002... 

Glover ED, Leischow SJ, Rennard SI, et al A smoking cessation trial with lobeline sulfate a pilot study. Am J Health Behav 22 62-74, 1998 Gourlay SG, Benowitz NL Is clonidine an effective smoking cessation therapy Drugs 50 197-207, 1995... 

Eyerman, D.J., Yamamoto, B.K. Lobeline attenuates methamphetamine-induced changes in vesicular monoamine transporter 2 immunoreactivity and monoamine depletions in the striatum. J. Pharmacol. Exp. Ther. 312 160, 2005. 

Harrod, S.B., Dwoskin, L.P., Crooks, P.A., Klebaur, J.E., Bardo, M.T. Lobeline attenuates self-administration in rats. J. Pharmacol. Exp. Ther. 298 172, 2001. 

Lendvai, B., Sershen, H., Lajtha, A. et al. Differential mechanisms involved in the effect of nicotinic agonists DMPP and lobeline to release [3H]5-HT from rat hippocampal slices. Neuropharmacology. 35 1769, 1996. 

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