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Picrotoxin for vertigo control in Ménière’s disease and other peripheral vestibular disorders: a systematic review

Published online by Cambridge University Press:  14 July 2025

Stefan Lyutenski*
Affiliation:
Department of Otorhinolaryngology, Helios Hospital Berlin-Buch, Berlin, Germany
Paul James
Affiliation:
Department of Otorhinolaryngology, Helios Hospital Berlin-Buch, Berlin, Germany
Marc Bloching
Affiliation:
Department of Otorhinolaryngology, Helios Hospital Berlin-Buch, Berlin, Germany
*
Corresponding author: Stefan Lyutenski; Email: s_lyutenski@gmx.de

Abstract

Objectives

The aim of this study is to systematically review and analyse the literature regarding clinical application of picrotoxin for vertigo caused by peripheral vestibular disorders.

Methods

We conducted a search in PubMed/MEDLINE and Google Scholar in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses recommendations. The primary selection included all studies exploring the effect of this phytopharmacological substance on the vestibular system and vertigo. The secondary selection included only reports on its clinical use for treatment of Ménière’s disease and other peripheral vestibular disorders.

Results

From the 398 identified studies, 18 were included from the primary selection and 6 from the secondary selection. In total, 203 patients received picrotoxin; 85 of them were treated for vertigo with 1-mg picrotoxin suppositories. In this subgroup vertigo was reduced in 74.9 per cent.

Conclusion

Picrotoxin is a non-invasive treatment option worth considering, especially in cochlear-implanted patients with recurring disabling vertigo.

Information

Type
Review Article
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of J.L.O. (1984) LIMITED.

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Footnotes

Stefan Lyutenski takes responsibility for the integrity of the content of the paper

References

Hänsel, R. Pflanzliche Mittel gegen Reisekrankheit. In: Hänsel, R, ed. Phytopharmaka, Grundlagen und Praxis. Berlin, Heidelberg: Springer, 1991;152–6CrossRefGoogle Scholar
Morton, J. Major Medicinal Plants: Botany, Culture, and Uses. Springfield, Illinois: Thomas, 1977Google Scholar
Drury, H. The Useful Plants of India. London: William H. Allen & Co., 1873Google Scholar
Clark, EP. The preparation of picrotoxin. J Am Chem Soc 1935;57:111110.1021/ja01309a047CrossRefGoogle Scholar
Felix, D, Ehrenberger, K. The action of GABA and acetylcholine in the labyrinth of the cat. In: Portmann, M, Aran, J-M, eds. Inner Ear Biology. Paris: Inserm, 1977;68:147–54Google Scholar
Ehrenberger, K, Benkoe, E, Felix, D. Suppressive action of picrotoxin, a GABA antagonist, on labyrinthine spontaneous nystagmus and vertigo in man. Acta Otolaryngol 1982;93:269–7310.3109/00016488209130882CrossRefGoogle ScholarPubMed
Moher, D, Liberati, A, Tetzlaff, J, Altman, DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e100009710.1371/journal.pmed.1000097CrossRefGoogle ScholarPubMed
Lopez-Escamez, JA, Carey, J, Chung, WH, Goebel, JA, Magnusson, M, Mandalà, M, et al. Diagnostic criteria for Menière’s disease. J Vestib Res 2015;25:1710.3233/VES-150549CrossRefGoogle ScholarPubMed
S2k-Leitlinie-Vestibuläre Funktionsstörungen AWMF (Version 1.0). [23 April 2024]Google Scholar
Segel, R. Herstellung von pikrotoxin-suppositorien. Die Österreichische Gsellschaft für Krankenhauspharmazie 1990:90;16Google Scholar
Weikert, S, Rotter, A, Scherer, H, Hölzl, M. Picrotoxin in the treatment of Menière’s disease [in German]. Laryngorhinootologie 2008;87:862–610.1055/s-2008-1077389CrossRefGoogle ScholarPubMed
Lucertini, M, Mirante, N, Casagrande, M, Trivelloni, P, Lugli, V. The effect of cinnarizine and Cocculus indicus on simulator sickness. Physiol Behav 2007;91:180–90CrossRefGoogle ScholarPubMed
Ehrenberger, K, Felix, D. Receptorpharmacological models for the therapy of labyrinthine vertigo. Acta Otolaryngol 1996;116:189–9110.3109/00016489609137820CrossRefGoogle ScholarPubMed
Enke, M. Die Wirkung von Picrotoxin auf den Physiologischen, Experimentellen und Pathologischen Nystagmus. Berlin: Freie Universität Berlin, 1996Google Scholar
Streinzer, W, Neuwirth-Riedl, K, Zrunek, M, Rasinger, GA, Fürpass, E, Ehrenberger, K. Die klinische Wertigkeit von Picrotoxin in der Behandlung peripher-vestibulärer Störungen. In: Majer, EH, ed. Die Oto- Rhino- Laryngologie in Kooperation mit Nachbardisziplinen: Österreichischer HNO-Kongress, Salzburg 1986. Wien: Faccultas-Universitätsverl, 1987;369–71Google Scholar
Weikert, S. Der Stellenwert von Picrotoxin, Elektrocochleographie und 3D-Endoskopie in der Diagnostik und Therapie Otolaryngologischer Erkrankungen. Medizinische Fakultät. Berlin: Cahrite – Universtiätsmedizin Berlin; 2019Google Scholar
Zabaneh, IS, Majerus, L, Olze, H, Stölzel, K. Picrotoxin in der Langzeittherapie des Morbus Menière – eine retrospektive Fallserie. Laryngorhinootologie 2023;102(suppl 2):S126Google Scholar
Cortes, C, Galindo, F, Galicia, S, Cebada, J, Flores, A. Excitatory actions of GABA in developing chick vestibular afferents: effects on resting electrical activity. Synapse 2013;67:374–8110.1002/syn.21646CrossRefGoogle ScholarPubMed
Felix, D, Ehrenberger, K. The action of putative neurotransmitter substances in the cat labyrinth. Acta Otolaryngol 1982;93:101–510.3109/00016488209130858CrossRefGoogle ScholarPubMed
Flock, A, Lam, DM. Neurotransmitter synthesis in inner ear and lateral line sense organs. Nature 1974;249:142–410.1038/249142a0CrossRefGoogle ScholarPubMed
Gavin, M, Blair, S. Modification of the macaque’s vestibulo-ocular reflex by picrotoxin. Arch Otolaryngol 1981;107:372–610.1001/archotol.1981.00790420046010CrossRefGoogle ScholarPubMed
Guth, SL, Norris, CH. Pharmacology of the isolated semicircular canal: effect of GABA and picrotoxin. Exp Brain Res 1984;56:72–810.1007/BF00237443CrossRefGoogle ScholarPubMed
Ishikawa, M, Miyazaki, H, Fukuda, H. Modulatory roles of GABAergic mechanisms in post-rotatory nystagmus in the rabbit. Gen Pharmacol 1989;20:229–3210.1016/0306-3623(89)90021-9CrossRefGoogle ScholarPubMed
Ito, M, Nisimaru, N, Yamamoto, M. Postsynaptic inhibition of oculomotor neurons involved in vestibulo-ocular reflexes arising from semicircular canals of rabbits. Exp Brain Res 1976;24:273–83Google ScholarPubMed
Lapeyre, PN, Kolston, PJ, Ashmore, JF. GABAB-mediated modulation of ionic conductances in type I hair cells isolated from guinea-pig semicircular canals. Brain Res 1993;609:269–7610.1016/0006-8993(93)90882-NCrossRefGoogle ScholarPubMed
Pantoja, AM, Holt, JC, Guth, PS. A role for chloride in the suppressive effect of acetylcholine on afferent vestibular activity. Hear Res 1997;112:213210.1016/S0378-5955(97)00101-9CrossRefGoogle ScholarPubMed
Ross, EL, Fish, MW, Olsen, A. Effects of some drugs on the vestibular response to rotation. Arch Otolaryngol Head Neck Surg 1931;14:755–7410.1001/archotol.1931.03580020846005CrossRefGoogle Scholar
Vega, R, Soto, E, Budelli, R, González-Estrada, MT. Is GABA an afferent transmitter in the vestibular system? Hear Res 1987;29:163–710.1016/0378-5955(87)90164-XCrossRefGoogle ScholarPubMed
Helling, K, Scherer, H. Vertigo attacks—current therapy [in German]. Laryngorhinootologie 2005;84:838–4010.1055/s-2005-870499CrossRefGoogle ScholarPubMed
Ehrenberger, K. Principles of conservative therapy of peripheral and central disorders of equilibrium [in German]. HNO 1988;36:301–4Google ScholarPubMed
Ehrenberger, K, Felix, D. Peripher Labyrinthäre Schwindelformen: Transmitterantagonisten als Therapeutikum. In: Westhofen, M, ed. Vestibularfunktion. Wien, New York: Springer, 2005;63–6Google Scholar
Felix, D, Ehrenberger, K. The action of putative neurotransmitter substances in the mamalian labyrinth. In: Drescher, DG, ed. Auditory Biochemistry. Springfield: Charles E. Thomas, 1985;68Google Scholar
Ariel, M, Robinson, FR, Knapp, AG. Analysis of vertebrate eye movements following intravitreal drug injections. II. Spontaneous nystagmus induced by picrotoxin is mediated subcortically. J Neurophysiol 1988;60:1022–3510.1152/jn.1988.60.3.1022CrossRefGoogle ScholarPubMed
Scherer, H. Das Gleichgewicht, 2nd edn. Berlin: Springer, 1997 10.1007/978-3-642-60371-6CrossRefGoogle Scholar
Murofushi, T, Tsubota, M, Kitao, K, Yoshimura, E. Simultaneous presentation of definite vestibular migraine and definite Ménière’s disease: overlapping syndrome of two diseases. Front Neurol 2018;9:74910.3389/fneur.2018.00749CrossRefGoogle ScholarPubMed
Pérez-Carbonell, T, Orts-Alborch, M, Pla-Gil, I, Pérez-Guilén, V, Tenías-Burrillo, JM, Marco-Algarra, J, et al. Bilateral Ménière’s disease according to its form of debut: synchronous and metachronous disease. J Laryngol Otol 2023;137:782–810.1017/S0022215122002262CrossRefGoogle ScholarPubMed
Schaaf, H. Morbus Menière Schwindel – Hörverlust – Tinnitus: Eine Psychosomatisch Orientierte Darstellung, 8th edn: Berlin, Springer, 2017 10.1007/978-3-662-52976-8CrossRefGoogle Scholar
Dimitriadis, PA, Zis, P. Nocebo effect in Menière’s disease: a meta-analysis of placebo-controlled randomized controlled trials. Otol Neurotol 2017;38:1370–510.1097/MAO.0000000000001555CrossRefGoogle ScholarPubMed
Taniguchi, AN, Sutton, SR, Mills, JF, Nguyen, SA, Rizk, HG, Meyer, TA, et al. Placebo effect in randomized controlled trials for Meniere’s disease: a meta-analysis. Am J Otolaryngol 2024;45:10417810.1016/j.amjoto.2023.104178CrossRefGoogle ScholarPubMed
Wax, PM. Analeptic use in clinical toxicology: a historical appraisal. J Toxicol Clin Toxicol 1997;35:203–910.3109/15563659709001195CrossRefGoogle ScholarPubMed
Bause, GS. From fish poison to merck picrotoxin. Anesthesiology 2013;118:126310.1097/ALN.0b013e31829a0b4bCrossRefGoogle ScholarPubMed
Koppanyi, T, Fazekas, JF. Acute barbiturate poisoning; analysis and evaluation of current therapy. Am J Med Sci 1950;220:559–7610.1097/00000441-195022050-00013CrossRefGoogle ScholarPubMed
Munch, JC, Ponce, AM. The bioassay of picrotoxin and Cocculus indicus preparations. J Am Pharm Assoc 1934;23:98104Google Scholar
Ito, Y, Lim, DK, Nabeshima, T, Ho, IK. Effects of picrotoxin treatment on GABAA receptor supramolecular complexes in rat brain. J Neurochem 1989;52:1064–7010.1111/j.1471-4159.1989.tb01848.xCrossRefGoogle ScholarPubMed
Pressly, B, Vasylieva, N, Barnych, B, Singh, V, Singh, L, Bruun, DA, et al. Comparison of the toxicokinetics of the convulsants picrotoxinin and tetramethylenedisulfotetramine (TETS) in mice. Arch Toxicol 2020;94:1995200710.1007/s00204-020-02728-zCrossRefGoogle ScholarPubMed
Cain, DP. Kindling by repeated intraperitoneal or intracerebral injection of picrotoxin transfers to electrical kindling. Exp Neurol 1987;97:243–5410.1016/0014-4886(87)90086-0CrossRefGoogle ScholarPubMed
Fernandez, F, Morishita, W, Zuniga, E, Nguyen, J, Blank, M, Malenka, RC, et al. Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat Neurosci 2007;10:411–1310.1038/nn1860CrossRefGoogle Scholar
Yoshiike, Y, Kimura, T, Yamashita, S, Furudate, H, Mizoroki, T, Murayama, M, et al. GABA(A) receptor-mediated acceleration of aging-associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin. PLoS One 2008;3:e3029CrossRefGoogle ScholarPubMed
Kotajima-Murakami, H, Hagihara, H, Sato, A, Hagino, Y, Tanaka, M, Katoh, Y, et al. Exposure to GABAA receptor antagonist picrotoxin in pregnant mice causes autism-like behaviors and aberrant gene expression in offspring. Front Psychiatry 2022;13:82135410.3389/fpsyt.2022.821354CrossRefGoogle ScholarPubMed
Teodorov, E, Habr-Alencar, SF, Sider, LH, Felicio, LF, Varoli, FM, Bernardi, MM. Prenatal treatment with picrotoxin promotes heterotypical sexual behavioral and neurochemical changes in male rat offspring. Brain Res 2006;1069:113–1910.1016/j.brainres.2005.11.006CrossRefGoogle ScholarPubMed
Meza, G. Gaba as an afferent neurotransmitter in the vestibular sensory periphery of vertebrates. Neurobiology (Bp) 1998;6:109–25Google Scholar
López, I, Wu, JY, Meza, G. Immunocytochemical evidence for an afferent GABAergic neurotransmission in the guinea pig vestibular system. Brain Res 1992;589:341–810.1016/0006-8993(92)91297-RCrossRefGoogle ScholarPubMed
Stupp, H, Küpper, K, Lagler, F, Sous, H, Quante, M. Inner ear concentrations and ototoxicity of different antibiotics in local and systemic application. Audiology 1973;12:350–6310.3109/00206097309071650CrossRefGoogle ScholarPubMed
Zolkowska, D, Banks, CN, Dhir, A, Inceoglu, B, Sanborn, JR, McCoy, MR, et al. Characterization of seizures induced by acute and repeated exposure to tetramethylenedisulfotetramine. J Pharmacol Exp Ther 2012;341:435–4610.1124/jpet.111.190579CrossRefGoogle ScholarPubMed