Alkaloids ibotenic acid

Inhibitory glutamate receptors (iGlu-Rs) are inhibitory, Glu-gated ion channels related to the ionotropic GABA receptors and glycine receptors, the open channel being permeable to Cl- and sometimes to K+. The isoxazole alkaloid ibotenic acid activates iGlu-Rs (Table 3.3). 

A review concerning the chemistry, biogenesis, and pharmacology of Amanita muscaria components includes a comprehensive coverage of the muscarine alkaloids. (+)-i -4-Hydroxypyrrolidin-2-one has been isolated from this source. A method for the identification of stereoisomeric muscarines by combination vacuum pyrolysis-g.c. analysis has been described. A micro method for the determination of ibotenic acid and other 3-hydroxyisoxazoles has been developed. Stereospecific syntheses for DL-muscarine and DL-a//o-muscarine have been reported. Pyrolysis of (1) yielded the carboxylic acid (2) and the bromolactone (3) which served as key compounds in the synthesis of the muscarines. The minor component (3) was shown to be an intermediate in the formation of (2) and therefore the conversion [(3)- -(2)] could be written as an intramolecular Sn2 displacement on an a-lactone (4). However, treatment of (3) with... 

On account of its high pharmacodynamic activity, ibotenic acid may be regarded as an essential component of the active principle of Amanita muscaria. This alkaloid, accompanied by related muscimol and musca-zone, has also been found in other mushrooms in which the occurrence of muscarines has not been recorded. 

In the mid-1960s investigations carried out independently by four research groups led to the isolation and subsequent structure elucidation from Amanita muscaria, A. strobiliformis, and A. pantherina of three fly-killing and narcosis potentiating compounds muscimol 37-40), ibotenic acid 40-44), and muscazone 43-47). At the same time tricholomic acid, another insecticidal constituent, was found in Tricholoma musca-rium 48,49). The nomenclature commonly accepted for these alkaloids was proposed by Eugster and Takemoto 50). 

Extrapolation of these results also led to a reasonable explanation of the biogenesis of ibotenic acid and related alkaloids. However, since the... 

Alkaloids derived from glutamic acid, other than y-aminobutyric acid (GABA), include kainic acid isolated from Digenea simplex, domoic acid isolated from Chondria armata, acromelic acids isolated from Clitocybe acromelalga, ibotenic acid isolated from Amanita strobiliformis Amanita pantherina), and tricholomic acid isolated from Tricholoma musucaria, and are described in this chapter. 

Until recently, these alkaloids were considered to be unusual amino acids rather than alkaloids. These alkaloids are biosynthesized without passing through the process of decarboxylation, except for GABA and muscimol, which is secondarily produced from ibotenic acid. 

Muscarine was formerly considered to be the main active ingredient. However, the content of muscarine in these Amanita species was low, and although the parasympathetic nerve system excitement activity of muscarine is very high, the activity could not be explained solely by this component. As a result, ibotenic acid and muscimol, the decarboxylation product of ibotenic acid, were isolated as active components and characterized [2,3]. Muscimol was identified as the same constituent that had been named pan-therine or agarine previously [4].These alkaloids possess an isoxazole skeleton, and it seems that glutamic acid or glutamine is involved in their biosynthesis. 

Potent central nervous system inhibitory effects and GABA antagonism were reported for muscimol [5], and this alkaloid was synthesized [4,6,7]. On the other hand, it was shown that ibotenic acid, like kainic acid (see Section 6.2), possessed more potent neuronal excitement eflbcts than glutamic acid, and the activities of these alkaloids were 2-7 times and 8-80 times that of glutamic acid, respectively [8]. It can be considered that these alkaloids are derivatives of glutamic acid in which the conformation was fixed. These alkaloids are used as biological tools in neuroexcitatory experiments [9]. 

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