Physostigmine plants

Carbamate Insecticides. These are stmcturaUy optimi2ed derivatives of the unique plant alkaloid physostigmine [57-47-6] a cholinergic dmg isolated in 1864 from Phjsostigma venenosum (see Alkaloids) (17,24,35—39). The carbamates maybe considered synthetic derivatives of the synaptic neurotransmitter acetylcholine, with very low turnover numbers. The A/,A/-dimethylcarbamates of heterocycHc enols (36) and the Ai-methylcarbamates of a variety of substituted phenols (35) with a wide range of insecticidal activity were described in 1954 (35). The latter are the most widely used carbamate insecticides, and the A/-methylcatbamates of oximes have subsequentiy been found to be effective systemic insecticides. 

Physostigmine, an alkaloid obtained from a West African plant, is used in the treatment of glaucoma. Treatment of physostigmine with methyl iodide gives a quaternary ammonium salt. What is the structure of this salt ... 

Traditionally, plants are a rich source of AChE inhibitors. People from the Caucasus used bulbs of snowdrops Galanthus sp.) to treat forgetfulness [25]. The active compound in this plant has been isolated and called galanthamine. Other plant-derived AChE inhibitors used for treatment of Alzheimer s disease include Huperzine A from Huperzia serrata and Rivastigmine (Excelon). The latter is a derivative from physostigmine isolated from the calabar bean, Physos-tigma vmmosum. 

The classic cholinesterase inhibitor is the alkaloid physostigmine (6)/ eserine (7). It was first isolated from the calabar bean, the seeds of Physostigma venenosum. Many novel natural products with AchE-inhibifing properties have shown promise as therapeutics for AD. Some examples of such products (pure compounds/plant extracts or formulations) are briefly reviewed here. 

Extracts of plants have been used as insecticides by humans since before the time of the Romans. Some of these extracts have yielded compounds useful as sources (e.g., pyrethrins, rotenoids, alkaloids), others as models (e.g., pyrethrins, physostigmine) of commercial insecticides. Recent technological advances which facilitate the isolation and identification of the bioactive constituents of plants should ensure the continued usefulness of plant compounds in commercial insect control, both as sources and models of new insect control agents and also as components in host plant resistance mechanisms. The focus in this paper will be on several classes of compounds, including limonoids, chromenes, ellagitannins, and methyl ketones, which were found to be components of the natural defenses of both wild and cultivated plants and which may be useful in commercial insect control. 

Eserine (physostigmine) has a pyrroloindole skeleton. This alkaloid is used as an anticholinesterase drug, which is fairly important in the treatment of Alzheimer s disease. Eserine is synthesized in Physostigma venenosum and stored in the seeds of this leguminous plant. The synthesis pathway starts with tryptamine, which is transformed into eserine (Eigure 45). 

Physostigmine [fi zoe STIG meen] is an alkaloid (a nitrogenous compound found in plants) and a tertiary amine. It is a substrate for acetylcholinesterase, and forms a relatively stable enzyme-substrate intermediate that reversibly inactivates acetylcholinesterase. The result is potentiation of cholinergic activity throughout the body. 

The proof of structure of dehydroesermetholemethine gave considerable further support to the 3a-methylpyrrolo[2,3-6]indole structure for physostigmine proposed by Robinson. The Robinson structure for the alkaloid also was derived easily from tryptophan, thus offering an obvious biogenetic route of synthesis by the plant (this will be discussed in more detail later). 

The discovery of several important drugs can be traced back to the medicinal or ritual use of specific plants in a non-Western culture. Alkaloids like quinine, emetine, physostigmine and tubocurarine were all discovered because their plant producer had been identified for a particular activity by a native culture.74 The World Health Organization (WHO) has estimated that 80% of the world s population rely mainly on plant-based traditional medicine for their primary health.75 There is, therefore, an enormous past and current literature on the human use of plants. 

Neurotransmitter inactivation. A number of animal and plant agents act as ANTICHOLINESTERASES, so interfering with synaptic trasmission. These include fasciculins (Fasl, Fas2, FasS), which are peptide snake venoms, huperzine from a plant, onchidal from molluscs and physostigmine (eserine) from the calabar bean. 

Several representatives of carbamic acid esters are considered in the literature to be strongly toxic compounds. The main alkaloid of the plant Physostigma venenosa, physostigmine (1), and also prostigmine (2), which is of synthetic origin, are compounds with cholinergic action and are of importance in medicine. 

Physostigmine (also called eserine) is an alkaloid obtained from the leguminous plant Calabar or ordeal bean—the dried, ripe seed of Physostigma Venenosum Balfour, a perennial plant in tropical West Africa. The main alkaloid was first isolated from the seeds of the Calabar bean in a pure form in 1864 by Jobs and Hesse, who called it physostigmine. One year later, it was obtained in a crystalline form by Vee and LeVen, who called it eserine. Physostigmine (PHY) is the first anticholinesterase agent known to man and is used in the treatment of atropine-induced intoxication. 

Non-isoprenoid Tryptamines. The stems of Picrasma ailanthoides, from which plant canthine derivatives had previously been obtained, has now yielded 1-methoxycarbonyl- and l-hydroxymethyl-j5-carboline. The molecular shape of eserine (= physostigmine) in the crystal has been determined. The new evidence fits in well with information, summarized previously, from n.m.r. NOE measurements. More alkylations at the C-1 methyl of harmaline have been reported.The A -methyl derivative of 1,2,3,4,6,7,12,12b-octahydro-indolo[2,3-a]quinolizine has been isolated from cranberries. 

Because OP/CM in.secticidcs have been used extensively since parathion was developed, their mechanism of action has been the subject of intense investigations. Most of these mechanistic studies focused on ChE inhibition and metabo-li.sm in insects, mammals, and plants. Regarding the mechanism of functional changes, two groups of anti-ChEs other than insecticidal anti-ChEs were also studied extensively— that is, CMs such as physostigmine and neostigmine because... 

Despite the fact that physostigmine is an important pharmaceutical, no reports have appeared on efforts to produce this alkaloid by means of plant cell cultures. Daoust (737) reported the fermentative production of physostigmine by means of the microorganism Streptomyces griseofuscus. Iwasa et al. (738) employed Streptomyces pseudogriseo-lus for the production of physostigmine. Murao and Hayashi (739) isolated physostigmine and its N-8 nor derivative from Streptomyces sp. AH-4. 

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