Grayanotoxin: Difference between revisions

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==Pharmacology==

Grayanotoxins are a group of toxic [[Diterpene|diterpenes]] found in the ericacaeae family of plants <ref name=":0">Gunduz A, Turedi S, Russell RM, Ayaz FA. Clinical review of grayanotoxin/mad honey poisoning past and present. Clin Toxicol (Phila). 2008 Jun;46(5):437-42. doi: 10.1080/15563650701666306. PMID: 18568799.</ref>. More than 25 grayanotoxin isoforms have been isolated from [[rhododendron]], though grayanotoxin I and grayanotoxin III are considered to be the most responsible for the toxic pharmacological effects of grayanotoxin-containing plants.<ref>Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep;12(3):208-15. doi: 10.1007/s12012-012-9162-2. PMID: 22528814; PMCID: PMC3404272.</ref> Grayanotoxin I, as well as grayanotoxin III, act as [[Agonist|agonists]] of [[Neuron|voltage-gated sodium channels.]]<ref>Yuki T, Yamaoka K, Yakehiro M, Seyama I. State-dependent action of grayanotoxin I on Na(+) channels in frog ventricular myocytes. J Physiol. 2001 Aug 1;534(Pt 3):777-90. doi: 10.1111/j.1469-7793.2001.00777.x. PMID: 11483708; PMCID: PMC2278746.</ref><ref name=":1">Kim SE, Shin MC, Akaike N, Kim CJ. Presynaptic effects of grayanotoxin III on excitatory and inhibitory nerve terminals in rat ventromedial hypothalamic neurons. Neurotoxicology. 2010 Mar;31(2):230-8. doi: 10.1016/j.neuro.2009.12.006. Epub 2009 Dec 28. PMID: 20038438.</ref> Through this mechanism, grayanotoxins increase the release of [[Neurotransmitter|neurotransmitters]] in the central nervous system such as [[GABA]] <ref name=":1" />, [[glutamate]] <ref name=":1" />, and [[acetylcholine]] <ref>Pischon H, Petrick A, Müller M, Köster N, Pietsch J, Mundhenk L. Grayanotoxin I Intoxication in Pet Pigs. ''Veterinary Pathology''. 2018;55(6):896-899. doi:10.1177/0300985818789482</ref>. Additionally, grayanotoxin III may act as an [[antagonist]] of [[Glutamate|central glutamate receptors]], further contributing to [[Depressant|CNS depressant]] effects <ref>Ohgaki T, Uchida S, Meguri H, Ogita K, Yoneda Y. Preventive action of quisqualic acid against grayanotoxin-induced suppression of locomotor activity in mice. Neuropharmacology. 1988 Oct;27(10):1045-53. doi: 10.1016/0028-3908(88)90066-4. PMID: 3070432.</ref>. Reports of grayanotoxin intoxication include symptoms of the [[Cholinergics|cholinergic]] toxidrome such as [[Decreased heart rate|decreased heart rate]], [[Decreased blood pressure|hypotension]], and an [[Cognitive effects|altered mental status]] <ref name=":0" />.

Grayanotoxins are a group of toxic [[Diterpene|diterpenes]] found in the ericacaeae family of plants <ref name=":0">Gunduz A, Turedi S, Russell RM, Ayaz FA. Clinical review of grayanotoxin/mad honey poisoning past and present. Clin Toxicol (Phila). 2008 Jun;46(5):437-42. doi: 10.1080/15563650701666306. PMID: 18568799.</ref>. More than 25 grayanotoxin isoforms have been isolated from [[rhododendron]], though grayanotoxin I and grayanotoxin III are considered to be the most responsible for the toxic pharmacological effects of grayanotoxin-containing plants.<ref>Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep;12(3):208-15. doi: 10.1007/s12012-012-9162-2. PMID: 22528814; PMCID: PMC3404272.</ref> Grayanotoxin I, as well as grayanotoxin III, act as [[Agonist|agonists]] of [[Neuron|voltage-gated sodium channels.]]<ref>Yuki T, Yamaoka K, Yakehiro M, Seyama I. State-dependent action of grayanotoxin I on Na(+) channels in frog ventricular myocytes. J Physiol. 2001 Aug 1;534(Pt 3):777-90. doi: 10.1111/j.1469-7793.2001.00777.x. PMID: 11483708; PMCID: PMC2278746.</ref><ref name=":1">Kim SE, Shin MC, Akaike N, Kim CJ. Presynaptic effects of grayanotoxin III on excitatory and inhibitory nerve terminals in rat ventromedial hypothalamic neurons. Neurotoxicology. 2010 Mar;31(2):230-8. doi: 10.1016/j.neuro.2009.12.006. Epub 2009 Dec 28. PMID: 20038438.</ref> Through this mechanism, grayanotoxins increase the release of [[Neurotransmitter|neurotransmitters]] in the central nervous system such as [[GABA]] <ref name=":1" />, [[glutamate]] <ref name=":1" />, and [[acetylcholine]] <ref>Pischon H, Petrick A, Müller M, Köster N, Pietsch J, Mundhenk L. Grayanotoxin I Intoxication in Pet Pigs. ''Veterinary Pathology''. 2018;55(6):896-899. doi:10.1177/0300985818789482</ref>.

Additionally, grayanotoxin III may act as an [[antagonist]] of [[Glutamate|central glutamate receptors]], further contributing to [[Depressant|CNS depressant]] effects <ref>Ohgaki T, Uchida S, Meguri H, Ogita K, Yoneda Y. Preventive action of quisqualic acid against grayanotoxin-induced suppression of locomotor activity in mice. Neuropharmacology. 1988 Oct;27(10):1045-53. doi: 10.1016/0028-3908(88)90066-4. PMID: 3070432.</ref>. Reports of grayanotoxin intoxication include symptoms of the [[Cholinergics|cholinergic]] toxidrome such as [[Decreased heart rate|decreased heart rate]], [[Decreased blood pressure|hypotension]], and an [[Cognitive effects|altered mental status]] <ref name=":0" />.

==Subjective effects==

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 ==Pharmacology==
 {{pharmacology}}
-Grayanotoxins are a group of toxic [[Diterpene|diterpenes]] found in the ericacaeae family of plants <ref name=":0">Gunduz A, Turedi S, Russell RM, Ayaz FA. Clinical review of grayanotoxin/mad honey poisoning past and present. Clin Toxicol (Phila). 2008 Jun;46(5):437-42. doi: 10.1080/15563650701666306. PMID: 18568799.</ref>. More than 25 grayanotoxin isoforms have been isolated from [[rhododendron]], though grayanotoxin I and grayanotoxin III are considered to be the most responsible for the toxic pharmacological effects of grayanotoxin-containing plants.<ref>Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep;12(3):208-15. doi: 10.1007/s12012-012-9162-2. PMID: 22528814; PMCID: PMC3404272.</ref> Grayanotoxin I, as well as grayanotoxin III, act as [[Agonist|agonists]] of [[Neuron|voltage-gated sodium channels.]]<ref>Yuki T, Yamaoka K, Yakehiro M, Seyama I. State-dependent action of grayanotoxin I on Na(+) channels in frog ventricular myocytes. J Physiol. 2001 Aug 1;534(Pt 3):777-90. doi: 10.1111/j.1469-7793.2001.00777.x. PMID: 11483708; PMCID: PMC2278746.</ref><ref name=":1">Kim SE, Shin MC, Akaike N, Kim CJ. Presynaptic effects of grayanotoxin III on excitatory and inhibitory nerve terminals in rat ventromedial hypothalamic neurons. Neurotoxicology. 2010 Mar;31(2):230-8. doi: 10.1016/j.neuro.2009.12.006. Epub 2009 Dec 28. PMID: 20038438.</ref> Through this mechanism, grayanotoxins increase the release of [[Neurotransmitter|neurotransmitters]] in the central nervous system such as [[GABA]] <ref name=":1" />, [[glutamate]] <ref name=":1" />, and [[acetylcholine]] <ref>Pischon H, Petrick A, Müller M, Köster N, Pietsch J, Mundhenk L. Grayanotoxin I Intoxication in Pet Pigs. ''Veterinary Pathology''. 2018;55(6):896-899. doi:10.1177/0300985818789482</ref>. Additionally, grayanotoxin III may act as an [[antagonist]] of [[Glutamate|central glutamate receptors]], further contributing to [[Depressant|CNS depressant]] effects <ref>Ohgaki T, Uchida S, Meguri H, Ogita K, Yoneda Y. Preventive action of quisqualic acid against grayanotoxin-induced suppression of locomotor activity in mice. Neuropharmacology. 1988 Oct;27(10):1045-53. doi: 10.1016/0028-3908(88)90066-4. PMID: 3070432.</ref>. Reports of grayanotoxin intoxication include symptoms of the [[Cholinergics|cholinergic]] toxidrome such as [[Decreased heart rate|decreased heart rate]], [[Decreased blood pressure|hypotension]], and an [[Cognitive effects|altered mental status]] <ref name=":0" />.
+Grayanotoxins are a group of toxic [[Diterpene|diterpenes]] found in the ericacaeae family of plants <ref name=":0">Gunduz A, Turedi S, Russell RM, Ayaz FA. Clinical review of grayanotoxin/mad honey poisoning past and present. Clin Toxicol (Phila). 2008 Jun;46(5):437-42. doi: 10.1080/15563650701666306. PMID: 18568799.</ref>. More than 25 grayanotoxin isoforms have been isolated from [[rhododendron]], though grayanotoxin I and grayanotoxin III are considered to be the most responsible for the toxic pharmacological effects of grayanotoxin-containing plants.<ref>Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep;12(3):208-15. doi: 10.1007/s12012-012-9162-2. PMID: 22528814; PMCID: PMC3404272.</ref> Grayanotoxin I, as well as grayanotoxin III, act as [[Agonist|agonists]] of [[Neuron|voltage-gated sodium channels.]]<ref>Yuki T, Yamaoka K, Yakehiro M, Seyama I. State-dependent action of grayanotoxin I on Na(+) channels in frog ventricular myocytes. J Physiol. 2001 Aug 1;534(Pt 3):777-90. doi: 10.1111/j.1469-7793.2001.00777.x. PMID: 11483708; PMCID: PMC2278746.</ref><ref name=":1">Kim SE, Shin MC, Akaike N, Kim CJ. Presynaptic effects of grayanotoxin III on excitatory and inhibitory nerve terminals in rat ventromedial hypothalamic neurons. Neurotoxicology. 2010 Mar;31(2):230-8. doi: 10.1016/j.neuro.2009.12.006. Epub 2009 Dec 28. PMID: 20038438.</ref> Through this mechanism, grayanotoxins increase the release of [[Neurotransmitter|neurotransmitters]] in the central nervous system such as [[GABA]] <ref name=":1" />, [[glutamate]] <ref name=":1" />, and [[acetylcholine]] <ref>Pischon H, Petrick A, Müller M, Köster N, Pietsch J, Mundhenk L. Grayanotoxin I Intoxication in Pet Pigs. ''Veterinary Pathology''. 2018;55(6):896-899. doi:10.1177/0300985818789482</ref>.
+Additionally, grayanotoxin III may act as an [[antagonist]] of [[Glutamate|central glutamate receptors]], further contributing to [[Depressant|CNS depressant]] effects <ref>Ohgaki T, Uchida S, Meguri H, Ogita K, Yoneda Y. Preventive action of quisqualic acid against grayanotoxin-induced suppression of locomotor activity in mice. Neuropharmacology. 1988 Oct;27(10):1045-53. doi: 10.1016/0028-3908(88)90066-4. PMID: 3070432.</ref>. Reports of grayanotoxin intoxication include symptoms of the [[Cholinergics|cholinergic]] toxidrome such as [[Decreased heart rate|decreased heart rate]], [[Decreased blood pressure|hypotension]], and an [[Cognitive effects|altered mental status]] <ref name=":0" />.
 ==Subjective effects==