Ibotenic acid is a neurotoxin that has agonist activity at both N-methyl-D-aspartate (NMDA) and trans-ACPD or metabolite quisqualate (Qm) receptor sites[1]. Ibotenic acid is structurally similar to glutamate and can penetrate the blood-brain barrier. Once in the central nervous system, Ibotenic acid undergoes decarboxylation to form muscimol, which has structural similarity to gamma-aminobutyric acid (GABA) and acts as a potent agonist at GABAA receptors[2, 3]. Ibotenic acid can induce degeneration of hippocampal neurons and can also be used to construct experimental animal models of neurological injury, such as schizophrenia models[4, 5].
In vivo, Ibotenic acid (16mg/kg, 1mg/mL) was injected intraperitoneally into mice for 20min, 1h, and 4h, respectively. Glutamate levels in the hippocampus and brainstem of mice decreased significantly 4h after intoxication, adrenaline levels in the cerebral cortex decreased at 20min after intoxication, and tyrosine levels in the brainstem and cerebellum decreased after 4h. Acute exposure also inhibited the motor activity of mice[6].
References:
[1] Zinkand W C, Moore W C, Thompson C, et al. Ibotenic acid mediates neurotoxicity and phosphoinositide hydrolysis by independent receptor mechanisms[J]. Molecular and chemical neuropathology, 1992, 16(1): 1-10.
[2] Stebelska K. Fungal hallucinogens psilocin, ibotenic acid, and muscimol: analytical methods and biologic activities[J]. Therapeutic Drug Monitoring, 2013, 35(4): 420-442.
[3] Issahaku A R, Wilhelm A, Schutte-Smith M, et al. Elucidating the binding mechanisms of GABA and Muscimol as an avenue to discover novel GABA-mimetic small molecules[J]. Journal of Biomolecular Structure and Dynamics, 2024: 1-16.
[4] Heo H, Shin Y, Cho W, et al. Memory improvement in ibotenic acid induced model rats by extracts of Scutellaria baicalensis[J]. Journal of ethnopharmacology, 2009, 122(1): 20-27.
[5] Becker A, Grecksch G, Bernstein H G, et al. Social behaviour in rats lesioned with ibotenic acid in the hippocampus: quantitative and qualitative analysis[J]. Psychopharmacology, 1999, 144(4): 333-338.
[6] Dai R, Duan Z, Han B, et al. Preliminary study on the time-correlation changes in brain neurotransmitters of mice exposed to mushroom toxin ibotenic acid[J]. Frontiers in Neuroscience, 2025, 19: 1561291.
Ibotenic acid是一种神经毒素，对N-甲基-D-天冬氨酸（NMDA）和反式ACPD或代谢使君子酸（Qm）受体位点均具有激动剂活性[1]。Ibotenic acid在结构上类似于谷氨酸，可以穿透血脑屏障，一旦进入中枢神经系统，Ibotenic acid经历脱羧以形成蝇蕈醇（muscimol），蝇蕈醇具有与γ-氨基丁酸（GABA）的结构相似性并且充当GABAA受体的有效激动剂[2, 3]。Ibotenic acid能够诱导海马神经元的变性，还能够用于构建实验动物神经损伤模型，例如精神分裂症模型[4, 5]。
在体内，Ibotenic acid（16mg/kg, 1mg/mL）通过腹腔注射处理分别让小鼠中毒20min、1h和4h，小鼠海马和脑干中谷氨酸水平在中毒4h后显著降低，大脑皮层中肾上腺素水平在中毒20min时降低，而脑干和小脑中酪氨酸水平在4h后降低，且急性暴露抑制了小鼠的运动活动[6]。