Browse history interactively

Page 1

Page 1Revision 1

Page 2

Page 2Revision 2

← Previous editContent deleted Content addedVisualWikitext

Revision as of 11:03, 19 January 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,071 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: ChEMBL KEGG.← Previous edit		Latest revision as of 16:12, 25 December 2024 edit undo86.144.233.203 (talk)No edit summary
(264 intermediate revisions by more than 100 users not shown)
Line 1:		Line 1:
			{{Short description|Chemical compound}}
	{{Drugbox		{{Drugbox
			| Watchedfields = changed
	| verifiedrevid = 399901251
			| verifiedrevid = 408765419
	| IUPAC_name = 6-allyl-4-methoxy-1,3-benzodioxole
			| IUPAC_name = 7-Allyl-5-methoxy-1,3-benzodioxole
	| image = Myristicin.svg
			| image = Myristicin.svg
	| width = 200
			| width = 200
	| image2 = Myristicin_3d_structure.png
			| image2 = Myristicin-3D-balls.png
	| width = 200
			<!--Clinical data-->
	| KEGG = C10480
			| legal_UK = PSA
	| InChI = 1/C11H12O3/c1-3-4-8-5-9(12-2)11-10(6-8)13-7-14-11/h3,5-6H,1,4,7H2,2H3
			| legal_US = Unscheduled.
	| InChIKey = BNWJOHGLIBDBOB-UHFFFAOYAE
			| legal_UN = Unscheduled.
	| ChEMBL = 481044
			| legal_status = In general: uncontrolled
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| dependency_liability = None
	| StdInChI = 1S/C11H12O3/c1-3-4-8-5-9(12-2)11-10(6-8)13-7-14-11/h3,5-6H,1,4,7H2,2H3
			| addiction_liability = Low
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| routes_of_administration = Oral (nutmeg); Insufflated (pure myristicin)
	| StdInChIKey = BNWJOHGLIBDBOB-UHFFFAOYSA-N
			<!--Identifiers-->
	| CAS_number = 607-91-0
			| CAS_number_Ref = {{cascite|correct|??}}
	| ATC_prefix =
	| ATC_suffix =		| CAS_number = 607-91-0
	| PubChem = 4276		| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = 04PD6CT78W
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 4125		| PubChem = 4276
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| chemical_formula = C<sub>11</sub>H<sub>12</sub>O<sub>3</sub>
			| ChemSpiderID = 4125
	| molecular_weight = 192.21 g/mol
	| synonyms = 3-methoxy,4,5-methylenedioxy-allylbenzene		| KEGG_Ref = {{keggcite|correct|kegg}}
			| KEGG = C10480
	| smiles = O1c2cc(cc(OC)c2OC1)C\C=C
			| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| bioavailability =
	| protein_bound =		| ChEMBL = 481044
			<!--Chemical data-->
	| metabolism =
			| C = 11
	| elimination_half-life =
	| excretion =		| H = 12
			| O = 3
	| pregnancy_category=
	| legal_status = Uncontrolled		| smiles = O1c2cc(cc(OC)c2OC1)C\C=C
			| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| routes_of_administration = Oral
			| StdInChI = 1S/C11H12O3/c1-3-4-8-5-9(12-2)11-10(6-8)13-7-14-11/h3,5-6H,1,4,7H2,2H3
			| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChIKey = BNWJOHGLIBDBOB-UHFFFAOYSA-N
			| synonyms = 3-methoxy-4,5-methylenedioxy-allylbenzene; 5-methoxy-3,4-methylenedioxy-allylbenzene
	}}		}}
			'''Myristicin''' is a naturally occurring compound (a ]) found in common herbs and spices, such as ].<ref name="pubchem">{{cite web |title=Myristicin |url=https://pubchem.ncbi.nlm.nih.gov/compound/4276 |publisher=PubChem, US National Library of Medicine |access-date=14 May 2023 |date=13 May 2023}}</ref><ref name="drugs">{{cite web |title=Nutmeg |url=https://www.drugs.com/npp/nutmeg.html |publisher=Drugs.com |access-date=14 May 2023 |date=21 November 2022}}</ref> It is an ], and has been shown to enhance the effectiveness of other insecticides.<ref name=pubchem/><ref name="Lichtenstein_1963">{{cite journal| vauthors = Lichtenstein EP, Casida JE |date=1963|title=Naturally Occurring Insecticides, Myristicin, an Insecticide and Synergist Occurring Naturally in the Edible Parts of Parsnips |journal=Journal of Agricultural and Food Chemistry|volume=11|issue=5|pages=410–415|doi=10.1021/jf60129a017 |bibcode=1963JAFC...11..410L }}</ref>
			When ingested, myristicin may produce ],<ref name=pubchem/><ref name="Stein_2001">{{cite journal | vauthors = Stein U, Greyer H, Hentschel H | title = Nutmeg (myristicin) poisoning—report on a fatal case and a series of cases recorded by a poison information centre | journal = Forensic Science International | volume = 118 | issue = 1 | pages = 87–90 | date = April 2001 | pmid = 11343860 | doi = 10.1016/s0379-0738(00)00369-8 }}</ref> and can be converted to ] in controlled chemical synthesis.<ref name="Clark_1996">{{cite journal| vauthors = Clark CR, DeRuiter J, Noggle FT |date=1996-01-01|title=Analysis of 1-(3-Methoxy-4,5-Methylenedioxyphenyl)-2-Propanamine (MMDA) Derivatives Synthesized from Nutmeg Oil and 3-Methoxy-4,5-Methylenedioxybenzaldehyde |journal=Journal of Chromatographic Science|volume=34|issue=1|pages=34–42|doi=10.1093/chromsci/34.1.34 |doi-access=free}}</ref> It interacts with many enzymes and signaling pathways in the body,<ref name="Lee_2005">{{cite journal | vauthors = Lee BK, Kim JH, Jung JW, Choi JW, Han ES, Lee SH, Ko KH, Ryu JH | display-authors = 6 | title = Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cells | journal = Toxicology Letters | volume = 157 | issue = 1 | pages = 49–56 | date = May 2005 | pmid = 15795093 | doi = 10.1016/j.toxlet.2005.01.012 }}</ref><ref name="Yang_2015">{{cite journal | vauthors = Yang AH, He X, Chen JX, He LN, Jin CH, Wang LL, Zhang FL, An LJ | display-authors = 6 | title = Identification and characterization of reactive metabolites in myristicin-mediated mechanism-based inhibition of CYP1A2 | journal = Chemico-Biological Interactions | volume = 237 | pages = 133–40 | date = July 2015 | pmid = 26091900 | doi = 10.1016/j.cbi.2015.06.018 | bibcode = 2015CBI...237..133Y }}</ref> and may have dose-dependent ] in living cells.<ref name="Lee_2005" /> Myristicin is listed in the ].<ref name=pubchem/>
	'''Myristicin''' is a ], a natural organic compound present in small amounts in the ] of ] and to a lesser extent in other spices such as ] and ]. Myristicin is a naturally occurring ] and ] with possible ] effects on ] cells.<ref>
	{{cite journal |author=Lee BK, Kim JH, Jung JW, Choi JW, Han ES, Lee SH, Ko KH, Ryu JH |title=Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cells |journal=Toxicol. Lett. |volume=157 |issue=1 |pages=49–56 |year=2005 |pmid=15795093 |doi=10.1016/j.toxlet.2005.01.012}}</ref> It has ] properties at doses much higher than used in ]. Myristicin is a weak inhibitor of ].<ref>{{cite journal |author=Truitt EB, Duritz G, Ebersberger EM |title=Evidence of monoamine oxidase inhibition by myristicin and nutmeg |journal=Proc. Soc. Exp. Biol. Med. |volume=112 |issue= |pages=647–50 |year=1963 |pmid=13994372}}</ref> Raw nutmeg produces ]-like symptoms, attributed to myristicin and ].<ref name="pmid15249817">{{cite journal | author = McKenna A, Nordt SP, Ryan J | title = Acute nutmeg poisoning | journal = European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine | volume = 11 | issue = 4 | pages = 240–1 | year = 2004 | month = August | pmid = 15249817 | doi = | url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0969-9546&volume=11&issue=4&spage=240}}</ref>
	== Uses ==		== Uses ==
			Isolated myristicin has proven an effective insecticide against many agricultural pests, including '']'' mosquito larvae, '']'' (hairy caterpillars),<ref name="Srivastava_2001" /> ''Epilachna varivestis'' (]s), '']'' (pea aphids), ]s, and '']'' (fruit flies). Myristicin was shown to be an effective repellent, and to cause mortality via direct and systemic exposure. It also displayed a ] effect when administered to insects in combination with existing insecticides.<ref name="Lichtenstein_1963" />
			The structure of myristicin closely resembles that of amphetamine compounds, and it is capable of producing psychotropic effects similar to ] compounds.<ref name=pubchem/> Because of this, it can be used in synthetic synthesis to create amphetamine derivatives, and create ] like ] that are similar in structure and effect to MDMA.<ref name="Clark_1996" /> Out of the common spices that contain myristicin, nutmeg has a high relative concentration of the compound,<ref name=drugs/> and therefore is used to exploit the effects of myristicin.<ref name=pubchem/><ref name=drugs/>
	In 1963, ] speculated myristicin could be ] to ], a psychoactive drug related to ], in the ].<ref> at lycaeum.org</ref> This speculation has never been confirmed and studies with the closely related compounds ] and ] demonstrated the proposed ] reactions did not take place in humans.
	<ref>{{cite journal
	| author = Björnstad K, Helander A, Hultén P, Beck O
	| title = Bioanalytical investigation of asarone in connection with Acorus calamus oil intoxications
	| journal = J Anal Toxicol
	| volume = 33
	| issue = 9
	| pages = 604–9
	| year = 2009
	| pmid = 20040135
	| doi =
	| url =
	}}</ref>.
			Furthermore, myristicin interferes with multiple signaling pathways and enzyme processes in the body.<ref name=pubchem/><ref name="Lee_2005" /><ref name="Yang_2015" />
	Intoxications with myristicin or ] ] have effects that vary from person to person, but are often reported to be a state somewhere between waking and dreaming; euphoria is reported and nausea is often experienced. Users also report bloodshot eyes and memory disturbances during nutmeg intoxication.<ref>See for various primary and secondary sources related to nutmeg/myristicin intoxication.</ref>
			== Sources of myristicin ==
	In addition to a semiconscious state, myristicin also has been known to induce psychoactive effects, such as visual distortions. The dose required to achieve such an effect varies from person to person and from source to source. Nutmeg intoxication has an extremely long time before peak is reached, sometimes taking up to seven hours, and effects can be felt for 24 hours, with lingering effects lasting up to 72 hours.<ref>http://www.erowid.org/plants/nutmeg/nutmeg_basics.shtml></ref><ref>http://www.erowid.org/experiences/subs/exp_Nutmeg.shtml></ref>
			Myristicin can be found in the ] of ], ], ],<ref name="MeaningTrees">{{cite q|Q118646408|pp=24-27}}</ref> and many members of the ] family, including ], ]s, ], ], ],<ref name="Rahman_2015">{{cite journal| vauthors = Rahman NA, Fazilah A, Effarizah ME | date=2015 |title=Toxicity of Nutmeg (Myristicin): A Review |journal=International Journal on Advanced Science, Engineering and Information Technology |volume=5 |issue=3 |pages=212–215 |doi=10.18517/ijaseit.5.3.518 |doi-access=free |citeseerx=10.1.1.920.6379 }}</ref> and ].<ref name="Lichtenstein_1963" />
			Trace amounts have also been isolated from a variety of plant species including '']'' (harvest fennel), species of the '']'' genus (water dropworts), species of the '']'' family (mint, sage, or deadnettle families), ''] (''Nepal camphor tree),<ref>{{cite journal | vauthors = Shulgin AT | title = Possible implication of myristicin as a psychotropic substance | journal = Nature | volume = 210 | issue = 5034 | pages = 380–384 | date = April 1966 | pmid = 5336379 | doi = 10.1038/210380a0 | bibcode = 1966Natur.210..380S | s2cid = 4189608 }}</ref> and ''Piper mullesua'' ("Hill Pepper").<ref name="Srivastava_2001">{{cite journal| vauthors = Srivastava S, Gupta MM, Prajapati V, Tripathi AK, Kumar S |date=2001|title=Insecticidal Activity of Myristicin from Piper mullesua |journal=Pharmaceutical Biology|language=en|volume=39|issue=3|pages=226–229|doi=10.1076/phbi.39.3.226.5933 |s2cid=83947896}}</ref>
	It should also be added that when consuming raw nutmeg, only 5-15% of the mass consumed is an essential oil fraction, of which only roughly 4% is myristicin,<ref>http://www.fao.org/docrep/v4084e/v4084e04.htm Nutmeg and derivatives.</ref> indicating the amount present overall in the nut is from 0.2-0.6%. While myristicin has been widely accepted as the main psychoactive component of nutmeg (along with elemicin), both the differences in subjective effects observed between nutmeg and synthetic myristicin, as well as the fact that myristicin is not a major component of the seed (therefore is possibly not present in high enough quantities) suggest it does not fully explain the effects of consuming raw nutmeg.<ref name="Campaign Science Working Group Review: Myristicin">http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/Myristicin.pdf Myristicin: Campaign Science Working Group Review.</ref>
			Depending on the conditions of growth and storage of the plant, a high quality nutmeg (''])'' seed can contain up to 13&nbsp;mg of myristicin per 1 gram.<ref>{{cite journal| vauthors = Nowak J, Woźniakiewicz M, Gładysz M, Sowa A, Kościelniak P |date=2015|title=Development of Advance Extraction Methods for the Extraction of Myristicin from Myristica fragrans |journal=Food Analytical Methods|language=en|volume=9|issue=5|pages=1246–1253|doi=10.1007/s12161-015-0300-x |doi-access=free}}</ref>
	There are also data to suggest myristicin can alter the toxicity and/or metabolic pathway of some compounds<ref name="Campaign Science Working Group Review: Myristicin">http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/Myristicin.pdf Myristicin: Campaign Science Working Group Review.</ref> and it is a weak ].
			== Physiological effects ==
	==Overdosage==
			=== Psychoactive effects ===
	Excessive usage of nutmeg has caused clinical intoxication, characterized by nausea, vomiting, dizziness, anxiety, headache, hallucinations and irrational behavior. Blood myristicin concentrations may be measured to confirm a diagnosis of poisoning. <ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1067-1068.</ref>
			At a minimum dose of about 5 grams of nutmeg powder, symptoms of nutmeg intoxication can begin to emerge.<ref name="Rahman_2015" /> Nutmeg intoxication may produce dizziness, drowsiness, and confusion, although in higher amounts, it may have effects similar to other ]s due to its ] effects.<ref name=pubchem/><ref>{{cite journal | vauthors = Roeters van Lennep JE, Schuit SC, van Bruchem-Visser RL, Özcan B | title = Unintentional nutmeg autointoxication | journal = The Netherlands Journal of Medicine | volume = 73 | issue = 1 | pages = 46–48 | date = January 2015 | pmid = 26219944 }}</ref>
	== See also ==		== Pharmacology ==
			Myristicin is additionally known to be a weak inhibitor of ] (MAO), an enzyme in humans that metabolizes neurotransmitters (for example, ], dopamine, epinephrine, and norepinephrine). It lacks the basic nitrogen atom that is typical of MAO inhibitors (]), potentially explaining a weaker inhibitory effect.<ref>{{cite journal | vauthors = Truitt EB, Duritz G, Ebersberger EM | title = Evidence of monoamine oxidase inhibition by myristicin and nutmeg | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 112 | issue = 3 | pages = 647–650 | date = March 1963 | pmid = 13994372 | doi = 10.3181/00379727-112-28128 | s2cid = 44996415 }}</ref>
	* ]
			While smaller concentrations of MAOIs may not cause problems, there are additional warnings regarding drug interactions. Those taking antidepressants that are ] (such as ], ], ] or ]<ref>{{cite web |title=Monoamine oxidase inhibitors (MAOIs) |url=https://www.mayoclinic.org/diseases-conditions/depression/in-depth/maois/art-20043992 |website=Mayo Clinic |date=12 September 2019 }}</ref>) or taking selective ] reuptake inhibiting (]) antidepressants should avoid essential oils rich in myristicin, such as that of nutmeg or anise.<ref>{{cite book |doi=10.1016/b978-0-443-06241-4.00004-7 |chapter=Kinetics and dosing |title=Essential Oil Safety |year=2014 | vauthors = Tisserand R, Young R |pages=39–67 |isbn=978-0-443-06241-4 |chapter-url=https://books.google.com/books?id=DbEKAQAAQBAJ&pg=PA39 }}</ref>
			=== Metabolites ===
			]
			Metabolism of myristicin yields 3-methoxycatechol<ref name=pubchem/> and enzymatically forms 5-allyl-1-methoxy-2,3-dihydroxybenzene (oxidation of the methylenedioxy group). Myristicin is also formed into demethylenylmyristicin, dihydroxymyristicin, and elemicin is formed into ''O''-demethylelemicin, ''O''-demethyldihydroxyelemicin, and safrole.<ref name=pubchem/>{{cn|date=May 2023}}
			== Chemistry ==
			]
			With a chemical structure resembling amphetamines and other precursors, myristicin can also be used to synthesize illicit hallucinogenic drugs. Under controlled conditions, myristicin isolated from nutmeg oil can be converted into MMDMA, a synthetic "designer drug" amphetamine derivative that is less potent than MDMA but produces comparable stimulant and hallucinogenic effects.<ref name="Clark_1996" />
			Myristicin is insoluble in water, and soluble in ], ], and ].<ref name=pubchem/>
			=== Toxicity ===
			In laboratory studies, myristicin is ]. Specifically, it stimulates ] release, which activates ] cascades and induces early ] in the cells.<ref name="Lee_2005"/> Myristicin has also been shown to inhibit ] enzymes, which are responsible for metabolizing a variety of substrates including hormones and toxins, allowing these substrates to accumulate.<ref name=pubchem/><ref name="Yang_2015" />
			The effects of nutmeg consumed in large doses are attributed mostly to myristicin: 1–7 hours following ingestion, symptoms include disorientation, giddiness, stupor, and stimulation of the ] leading to ].<ref name=pubchem/><ref name=drugs/> Also occurring are mild to intense ]s (similar to those induced by deliriants: walls and ceiling glitching or breathing), disorientation to time and surroundings, ], feelings of levitation, loss of consciousness, ], weak pulse, ], and ].<ref name=pubchem/> Symptoms of nutmeg intoxication further include nausea, abdominal pain, vomiting, minor to severe muscle spasms (severe in extreme overdose), headache, dryness of mouth, ] or ], ], ], and potentially death.<ref name=pubchem/><ref name=drugs/><ref name="Stein_2001" />
			Myristicin poisoning can be detected by testing levels of myristicin in the blood.<ref>{{cite book| vauthors = Baselt RC |title=Disposition of toxic drugs and chemicals in man|date=2008|publisher=Biomedical Publications|isbn=978-0-9626523-7-0|edition=8th|location=Foster City, CA|oclc=243548756}}{{pn|date=September 2021}}</ref> There are no known antidotes for myristicin poisoning, and treatment focuses on symptom management and potential sedation in cases of extreme ] or aggravation.<ref name=pubchem/><ref name = "Demetriades_2005">{{cite journal | vauthors = Demetriades AK, Wallman PD, McGuiness A, Gavalas MC | title = Low cost, high risk: accidental nutmeg intoxication | journal = Emergency Medicine Journal | volume = 22 | issue = 3 | pages = 223–225 | date = March 2005 | pmid = 15735280 | pmc = 1726685 | doi = 10.1136/emj.2002.004168 }}</ref>
	== References ==		== References ==
	{{Reflist|2}}		{{Reflist}}
	{{Hallucinogens}}		{{Hallucinogens}}
	{{Cholinergics}}
	{{phenylpropene}}		{{phenylpropene}}
			{{Authority control}}
			{{Use dmy dates|date=November 2024}}
	]		]
	]
	]
	]		]
			]
			]
			]
	]		]
	]		]
			]
	]
			]
	]
	]
	]
	]
	]
	]
	]
	]
	]
	]
	]
	]
	]
	]