Ibotenic Acid


Ibotenic acid is a psychoactive compound found in the mushroom Amanita muscaria.1 It is a prodrug of another compound in this species, muscimol. Muscimol is formed by the decarboxylation of ibotenic acid.

The Chemistry of Ibotenic Acid

Ibotenic acid is a conformationally-restricted isoxazole analog of the amino acid and excitatory neurotransmitter glutamic acid.2 It is a polar compound that is readily soluble in water.1

The Pharmacology of Ibotenic Acid

Ibotenic acid is an agonist of N-methyl-D-aspartic acid (NMDA) and trans-1-Amino-1,3 dicarboxycyclopentane (metabotropic quisqualate Qm) receptors.1 A 1992 study by Zinkand et al. found that the neurotoxicity of ibotenic acid comes from its activation of the NMDA receptors.3

The Applications and Potential of Ibotenic Acid

Ibotenic acid is used to create experimental brain lesions in rodents.4,5 Another application is for creating a rodent model for studying Alzheimer’s disease.6 Rats injected with ibotenic acid show a loss of neurons via the hippocampal performant pathway. These neuronal losses resemble the brain defects seen in Alzheimer’s disease.

  1. Stebelska K. Fungal hallucinogens psilocin, ibotenic acid, and muscimol: analytical methods and biologic activities. Therapeutic Drug Monitoring. 2013;35(4):420-442. doi:10.1097/FTD.0b013e31828741a5
  2. Michelot D, Melendez-Howell LM. Amanita muscaria: chemistry, biology, toxicology, and ethnomycology. Mycological Research. 2003;107(2):131-146. doi:10.1017/S0953756203007305
  3. Zinkand WC, Moore WC, Thompson C, Salama AI, Patel J. Ibotenic acid mediates neurotoxicity and phosphoinositide hydrolysis by independent receptor mechanisms. Molecular and Chemical Neuropathology. 1992;16(1):1-10. doi:10.1007/BF03159956
  4. Becker A, Grecksch G, Bernstein H-G, Höllt V, Bogerts B. Social behaviour in rats lesioned with ibotenic acid in the hippocampus: quantitative and qualitative analysis. Psychopharmacology. 1999;144(4):333-338. doi:10.1007/s002130051015
  5. Isacson O, Brundin P, Kelly P a. T, Gage FH, Björklund A. Functional neuronal replacement by grafted striatal neurones in the ibotenic acid-lesioned rat striatum. Nature. 1984;311(5985):458-460. doi:10.1038/311458a0
  6. Heo H, Shin Y, Cho W, Choi Y, Kim H, Kwon YK. Memory improvement in ibotenic acid induced model rats by extracts of Scutellaria baicalensis. Journal of Ethnopharmacology. 2009;122(1):20-27. doi:10.1016/j.jep.2008.11.026