Hemlock water dropwort poisoning

Ball, M.J.; Flather, Markus; Forfar, J C

doi:10.1136/pgmj.63.739.363

Cited by 20 publications

(8 citation statements)

References 5 publications

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“…The potent inhibition of GABAergic currents, known to play a crucial role in the inhibition in the adult CNS, would be an adequate explanation of the epileptogenic activity of OETX in the CNS (Chauvel et al. , 1978; Louvel and Heinemann, 1980; 1983; Ball et al. , 1987).…”

Section: Discussionmentioning

confidence: 99%

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Block and allosteric modulation of GABAergic currents by oenanthotoxin in rat cultured hippocampal neurons

Wyrembek

Lebida

Mercik

et al. 2010

British J Pharmacology

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Background and purpose: Oenanthotoxin (OETX), a polyacetylenic alcohol from plants of the genus Oenanthe, has recently been identified as potent inhibitor of GABA-evoked currents. However, the effects of OETX on the inhibitory postsynaptic currents (IPSCs), as well as the pharmacological mechanism(s) underlying its effects on GABAA receptors, remain unknown. The purpose of this study was to elucidate the mechanism underlying the inhibition of GABAergic currents by OETX. Experimental approach: Effects of OETX on GABAergic currents were studied using the patch clamp technique on rat cultured hippocampal neurons. Miniature IPSCs (mIPSCs) were recorded in the whole-cell configuration, while the current responses were elicited by ultrafast GABA applications onto the excised patches. Key results: OETX potently inhibited both mIPSCs and current responses, but its effect was much stronger on synaptic currents. Analysis of the effects of OETX on mIPSCs and evoked currents disclosed a complex mechanism: allosteric modulation of both GABAA receptor binding and gating properties and a non-competitive, probably open channel block mechanism. In particular, OETX reduced the binding rate and nearly abolished receptor desensitization. A combination of rapid clearance of synaptic GABA and OETX-induced slowing of binding kinetics is proposed to underlie the potent action of OETX on mIPSCs.Conclusions and implications: OETX shows a complex blocking mechanism of GABAA receptors, and the impact of this toxin is more potent on mIPSCs than on currents evoked by exogenous GABA. Such effects on GABAergic currents are compatible with the convulsions and epileptic-like activity reported for OETX.

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Section: Discussionmentioning

confidence: 99%

“…It seems that the most prominent action of OETX on the CNS is induction of epileptic‐like activity (see also Chauvel et al. , 1978; Louvel and Heinemann, 1980; 1983; Ball et al. , 1987).…”

Section: Introductionmentioning

confidence: 99%

Block and allosteric modulation of GABAergic currents by oenanthotoxin in rat cultured hippocampal neurons

Wyrembek

Lebida

Mercik

et al. 2010

British J Pharmacology

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“…Roots from C. maculata and O. crocata retain their toxicity long after harvesting and/or drying [25,26]. Although cicutoxin and oenanthotoxin are relatively unstable compounds on exposure to air, light, and heat, poisonings after ingestion of dried and/or cooked roots of both O. crocata and C. maculata have been reported [3,4,27,28]. Pharmacological studies by Grundy and Howarth have demonstrated marked toxicity with dried and powdered tubers of O. crocata [29].…”

Section: Biochemistry Of Active Compoundsmentioning

confidence: 99%

“…Other reported neurological symptoms include amnesia [2,12,26], parathesias [27], neuropsychological abnormalities [6], and hallucinations [12,44]. Electroencephalograms show diffuse abnormalities that may be persistent [6,12,13,26,27]. Coagulopathy has been reported on multiple occasions [9,26].…”

Section: Clinical Presentationmentioning

confidence: 99%

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Water Hemlock Poisoning

Cetaruk¹

2016

Critical Care Toxicology

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Water hemlock belongs to the family Apiaceae (Umbelliferae). The genus Cicuta includes the species spotted water hemlock (C. maculata), Western water hemlock (C. douglasii), and northern water hemlock also known as European water hemlock (C. virosa), C. bolanderi, C. bulbifera, C. californica, C. curtissii, C. mackenziana, C. occidentalis, and C. vagans (Figs. 1, 2, and 3). The active toxic compound in water hemlock is cicutoxin. The hemlock water dropwort (Oenanthe crocata) belongs to the family Apiaceae (Umbelliferae), genus Oenanthe. It is native to Europe but has been introduced to some parts of the United States. It lacks the chambered root of the Cicuta spp. and produces oenanthotoxin, a constitutional isomer (a compound that has the same molecular formula but a different structural formula) of cicutoxin. The various species of Cicuta and Oenanthe have approximately equivalent clinical toxicity at similar stages of plant growth, producing virtually identical clinical manifestations in poisoning, and, therefore, will be discussed as a single group. Common names of these plants include cowbane, children's bane, poison parsnip, five-fingered root, dead men's fingers, death-of-man, wild parsnip, snakeroot, snakeweed, beaver poison, muskrat weed, spotted hemlock, spotted cowbane, musquash root, false parsley, poison hemlock, wild carrot, fever root, mock-eel root, spotted parsley, cique vireuse, and carotte à moreau. Water hemlock species are biennial or perennial plants that grow to a height of 6-8 ft with

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Toxicant-Induced Rhabdomyolysis

Daubert¹

2017

Critical Care Toxicology

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Hemlock water dropwort poisoning

Cited by 20 publications

References 5 publications

Block and allosteric modulation of GABAergic currents by oenanthotoxin in rat cultured hippocampal neurons

Block and allosteric modulation of GABAergic currents by oenanthotoxin in rat cultured hippocampal neurons

Water Hemlock Poisoning

Toxicant-Induced Rhabdomyolysis

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