Arecaidine

Arecoline is usually stated to be present to the extent of 0-1 per cent., but Chemnitius gives the yield of hydrobromide as 0-35 to 0-4 per cent. Arecaidine and guvacine occur in smaller quantities, whilst guvacoline and arecolidine are found only in minute amounts. Alkaloidal assay processes for areca nuts have been published by Bourcet, and the National Formulary Committee, and Bond has described a method of estimation for arecoline hydrobromide. A microchemical test for the identification of arecoline has been devised by Gornyi. ... 

Liebbrandt have prepared arecaidine by bromination of methyl jV-methylpiperidine-3-carboxyIate, scission of hydrogen bromide from the resulting bromo-compound (VI) and hydrolysis of the resulting arecoline, but Preobrachenski and Fischer were unable to confirm this observation. 

Mannich has prepared arecaidine aldehyde (IV) by allowing a mixture of formaldehyde, acetaldehyde and methylamine hydrochloride to stand at 70° and pK 3. Some dialdehyde, MeN(CH2. CHa. CHO)2, is formed and this by loss of water produces arecaidine aldehyde. The latter is, converted into arecoline by the VVohl and Johnson process described above. 

Merck and Maeder have patented the manufacture of arecaidine by loss of water from l-methyl-4-hydroxypiperidine-3-carboxylic acid. A method of producing the latter has been describd by Mannich and Veit and has been developed by Ugriumov for the production of arecaidine and arecoline. With the same objective, Dankova, Sidorova and Preobrachenski use what is substantially McElvain s process,but start by converting ethylene oxide, via the chlorohydrin and the cyanohydrin, into -chloropropionic acid. The ethyl ester of this with methylamine in benzene at 140° furnishes methylbis(2-carbethoxyethyl) amine (I) which on refluxing with sodium or sodium Moamyloxide in xylene yields l-methyl-3-carbethoxy-4-piperidone (II). The latter is reduced by sodium amalgam in dilute hydrochloric acid at 0° to l-methyl-3-carbethoxy-4-hydroxypiperidine (III) which on dehydration, and hydrolysis, yields arecaidine (IV R = H), convertible by methylation into arecoline (IV R = CH3). 

Arecoline is hydrolysed by acids or alkalis to the corresponding acid, arecaidine, and conversely the latter, on esterification with methyl alcohol, yields arecoline, and vvith ethyl alcohol Ijomoarecoline. Syntheses of arecaidine, and therefore of arecoline, arc described above. 

Other examples of syntheses under physiological conditions will be found under arecaidine, lobelia, papaverine, cusparia bark alkaloids, harmala alkaloids, rutascarpine and yohimbine. 

FIGURE 7.7 Effect of the allosteric modulator ebumamonine on the potency of muscarinic agonists on m2 receptors. It can be seen that while no change in potency is observed for APE (arecaidine propargyl ester) pilocarpine is antagonized and arecoline is potentiated, illustrating the probe dependence of allosterism. From [1],... 

Arecaidine propargyl esther, 131 Arecoline, 131, 153 Amdt-Schulz law, 3 B-Arrestin, 84 Assays... 

Acetylcholine All four alkaloids derived from areca (arecoline, arecaidine, guvacoline, and guvacine) act as full agonists at muscarinic acetylcholine receptors (Wolf-Pflugmann et al. 1989). Peripherally administered arecoline (10 mg/kg) subtly reduces cortical and subcortical acetylcholine levels (Molinengo et al. 1986). 

Areca (Areca catechu) is a tall palm tree that yields a nut, commonly chewed in Asia for its stimulant effects. It is discussed at greater length in chapter 4, but is mentioned here briefly for its cognitive effects. Areca s psychoactive constituents (arecoline, arecaidine, guvacoline, and guvacine) are agonists at muscarinic acetylcholine receptors. They also directly inhibit reuptake of GABA. 

Lodge D, Johnston GA, Curtis DR, Brand SJ. (1977). Effects of the Areca nut constituents arecaidine and guvacine on the action of GABA in the cat central nervous system. Brain Res. 136(3) 513-22. 

Wess J, Lambrecht G, Moser U, Mutschler E. (1987). Stimulation of ganglionic muscarinic Ml receptors by a series of tertiary arecaidine and isoarecaidine esters in the pithed rat. EurJ Pharmacol. 134(1) 61-67. 

Wolf-Pflugmann M, Lambrecht G, Wess J, Mutschler E. (1989). Synthesis and muscarinic activity of a series of tertiary and quaternary N-substituted guvacine esters structurally related to arecoline and arecaidine propargyl ester. Arzneimittelforschung. 39(5) 539-44. 

The other alkaloids derived from nicotinic acid, with pyridine nucleus such as arecoline, arecaidine and guvacoline, are tetrahydronicotinic acid (guvacine) derivatives. 

Apomorphine 169, 170 Aporphine alkaloids 151, 152 Apparicine 16, 147 Arborine 105, 106 Arctigenin 39 Aren tin 41, 47 Arecaidine 86... 

The Michael acceptor can be an a, -unsaturated carboxylic ester. This possibility is illustrated with the conjugate addition of phenylmagnesium bromide to ethyl arecaidinate, which leads to 4-phenylnipecotic acid (equation 33). 

N.A. Arecoline, arecaine, arecaidine, arecolidine, isoguvacine, guvacine, givacoline, tannins, palmitic acid, stearic acid, myristic acid, lauric acid, margaric acid, nonadecanoid, heneicosanic acid.100 A breath sweetening masticatory, treat abdominal tumor, an astringent, stomachic, stimulant, and anthelmintic. 

The ester function of arecoline (159) is quantitatively hydrolyzed by both rat liver and brain homogenates to produce arecaidine (160) (determined by TLC anaylsis) (161). 

Seeds of Areca catechu (betel nut) (Palmae) contain the simple jV-methyltetrahydropyridine 3-carboxylic acid (jV-methyl-A -tetrahydronicotinic acid) arecaidine and arecoline (arecai-dine methyl ester) (Section 1, Appendix) that are mACh-R agonists and accordingly parasympathetic stimulants. Betel nut also yields guvacine (A -tetrahydronicotinic acid) that is an anti-epileptic GABA transport inhibitor. Conversely the jV-methyl dihydropyridone derivative ricinine from seeds of Ricinus communis (castor seed) (Euphorbiaceae) is a stimulatory agonist acting at the benzodiazepine site of the GABA(A) receptor. 

Arecaidine (= Arecaine) Areca catechu [betel nut] mACh-R agonist - atrial M2a ileal... 

Arecaidine (= Arecaine 1,2,5,6-Tetrahydro-1 -methyl-3-pyridinecarboxylic acid) (piperidine)... 

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