Ibotenate

Sallanon, M., Sakai, K., Buda, C., Puymartin, M. Jouvet, M. (1988). Increase of paradoxical sleep induced by microinjections of ibotenic acid into the ventrolateral part of the posterior hypothalamus in the cat. Arch. ltal. Biol. 126, 87-97. 

The value of muscimole as a psychedelic is diminished by the dizziness and muscle twitching which seem to occur (at least in some people), but a small dose in conjunction with another psychedelic should be very interesting. Ibotenic acid also occurs in Amanita, and though not itself a desirable psychedelic, it can be converted to muscimole by dissolving in dimethylsulfoxide or refluxing in water. 

The psychoactive constituents of fly agaric are amino acid derivatives (Eugster et al. 1965 Schultes and Flofman 1980, 1992). These include ibotenic acid, muscimol, muscazone, muscarine, and (R)-4-hydroxy-... 

The active constituents of amanita, and perhaps active metabolites as well, are excreted in urine. Because the mushrooms can be very expensive, many Siberian tribesmen drink their urine to prolong intoxication. Both ibotenic acid and muscimol are detected in urine. Up to 27% of muscimol injected into mice has been recovered from urine. 

Excitatory amino acids Ibotenic acid is structurally related to glutamate, the principal excitatory neurotransmitter, and it activates NMDA receptors (Madsen et al. 1990 Mayer and Westbrook 1987 Schwarcz et al. 1979 Honore et al. 1981). 

Ibotenate creates neurotoxic and phosphoinositide effects through distinct receptors (Zinkand et al. 1992). The neurotoxic effects are prevented by MK-801 and enhanced by glycine, implying NMDA involvement. Phosphoinositide hydrolysis is mediated by metabotropic receptors, and is unaffected by NMDA agents. 

Although they apparently differ in their mechanisms of action, ibotenic acid and muscimol apparently produce a qualitatively similar subjective and behavioral state (Schultes and Hofman 1980, 1992). However, muscimol is approximately 5 times as potent as ibotenic acid. Vegetative functions do not appear to be grossly affected at usual doses. 

Little is formally known about the toxicity of amanita use. Ibotenic acid is a potent neurotoxin, through excitatory amino acid mechanisms (Steiner et al. 1984 Schwarcz et al. 1984). It has been used extensively in animal research to create discrete neuroanatomical lesions. For example, it has been used to lesion the basal forebrain nuclei to create a putative animal model of Alzheimer s disease (Arbogast and Kozlowski 1988). 

Intracerebral injections of ibotenic acid produce cell loss in several cerebral areas, including the striatum, the hippocampus, substantia nigra, and piriform cortex (Schwarcz et al. 1979). This degeneration is limited to the site of injection and does not affect axons, passage, or synaptic terminals originating in other areas. 

Compared to other excitotoxic drugs, ibotenate has relatively lesser epileptogenic effects (Zaczek and Coyle 1982). However, intracerebroventricular infusion of ibotenic acid (6 nmol/min) induces clonic convulsions in mice (Laudrup and Klitgaard 1993). 

Arbogast RE, Kozlowski MR. (1988). Quantitative morphometric analysis of the neurotoxic effects of the excitotoxin, ibotenic acid, on the basal forebrain. /Veurotox/co/ogy Spring. 9(1) 39-45. 

Eugster CH, Muller GF, Good R. (1965). [The active ingredients from Amanita muscaria ibotenic acid and muscazone]. Tetrahedron Lett. 23 1813-15. 

Honore T, Krogsgaard-Larsen P, Hansen JJ, Lauridsen J. (1981). Glutamate and aspartate agonists structurally related to ibotenic acid. Molec Cell Blochem. 38 Spec. no. (pt 1) 123-28. 

NMDA receptor agonists derived from ibotenic acid. Preparation, neuroexcitation, and neurotoxicity. Eur J Pharmacoi. 189(6) 381-91. 

Scholz WK. (1994). An ibotenate-selective metabotropic glutamate receptor mediates protein phosphorylation in cultured hippocampal pyramidal neurons. J Neurochem. 62(5) 1764-72. 

Schwarcz R, Hokfelt T, Fuxe K, Jonsson G, Goldstein M, Terenius L. (1979). Ibotenic acid-induced neuronal degeneration a morphological and neurochemical study. Exp Brain Res. 37(2) 199-216. Schwartz RH. (1988). Mescaline a survey. Am Earn Physician. 37(4) 122-24. 

Steiner HX, McBean GJ, Kohier C, Roberts PJ, Schwarcz R. (1984). Ibotenate-induced neuronal degeneration in immature rat brain. Brain Res. 307(1-2) 117-24. 

Zinkand WC, Moore WC, Thompson C, Salama AI, Patel J. (1992). Ibotenic acid mediates neurotoxicity and phosphoinositide hydrolysis by independent receptor mechanisms. Mol Chem Neuropathol. 16(1-2) 1-10. 

Both toxins are isoxazole derivatives. In the mushroom, as well as in the eater, ibotenic acid (Figure 3.6a) is decarboxylated to muscimol (Figure 3.6b), which seems to be the active species. Muscimol is an agonist of GABA, and acts on the CNS in a way similar to diazepam. In animal experiments, both ibotenic acid and muscimol caused a decrease in muscle tone and motor activity, and an increase in brain levels of serotonine, but did not affect the cerebellar content of GABA. For a recent review on ibotenic acid and muscimol see Michelot and Melendez-Howell (2003). 

There is no specific treatment for ingestion of ibotenic acid or muscimol rather, treatment is symptomatic and supportive. Anxiety, hysteria, or convulsions can be treated with sedatives, such as diazepam. This should be done cautiously, however, and with the lowest effective dose because animal studies revealed that respiratory arrest may occur. In severe cases, with prolonged nausea, vomiting, or diarrhea, monitoring of fluid and electrolyte status may be required. Recent cases of muscarine poisonings were reported by Benjamin (1992), and Tupalska-Wilczynska et al. (1997). 

Muscarine is found in tiny amounts, usually under 20 pg/g, in other agaric genera, too, such as Amanita, Boletus, Hygrocybe, Lactarius, Mycena, and Russula. It was by the small amounts of muscarine present in A. muscaria, 90 pg/g, that the toxin was detected and identified (and got its name) but muscarine in A. muscaria usually does not account for the symptoms that occur after ingestion of this fungus, which are produced by muscimol and its precursor ibotenic acid. 

Muscimole from Ibotenic Acid. Reflux ibotenic acid in 10 times its weight of water. 

Stimulation - excitatory amino acids -headache, confusion, hallucinations Red alga (red tide), Green alga Mushrooms - Amanita family (fly agaric), flat pea [Lathyrus] Kainic acid, domoic acid -concentrated in shellfish, Ibotenic acid, muscarinic acid, (hallucinations) Latthyrism - motor neuron degeneration... 

Lu J, Zhang YH, Chou TC et al 2001 Contrasting effects of ibotenate lesions of the paraventricular nucleus and subparaventricular zone on sleep-wake cycle and temperature regulation. J Neurosci 21 4864-4874... 

A number of glutamate agonists including NMDA, kainate acid, quisqualic acid, and ibotenic acid, when applied locally, are able to destroy the cholinergic system. 

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