Myristicin
Template:Short description Template:Cs1 config Template:Drugbox Myristicin is a naturally occurring compound (an allylbenzene) found in common herbs and spices such as nutmeg.<ref name="pubchem">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="drugs">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is an insecticide, and has been shown to enhance the effectiveness of other insecticides.<ref name=pubchem/><ref name="Lichtenstein_1963">Template:Cite journal</ref>
When ingested in high doses, myristicin may produce hallucinogenic effects,<ref name=pubchem/><ref name=Hallström>Template:Cite journal</ref> and can be converted to MMDMA in controlled chemical synthesis.<ref name="Clark_1996">Template:Cite journal</ref> It interacts with many enzymes and signaling pathways in the body,<ref name="Lee_2005">Template:Cite journal</ref><ref name="Yang_2015">Template:Cite journal</ref> and may have dose-dependent cytotoxicity in living cells.<ref name="Lee_2005" /> Myristicin is listed in the Hazardous Substances Data Bank.<ref name=pubchem/>
UsesEdit
Isolated myristicin has proven an effective insecticide against many agricultural pests, including Aedes aegypti mosquito larvae, Spilosoma obliqua (hairy caterpillars),<ref name="Srivastava_2001" /> Epilachna varivestis (Mexican bean beetles), Acyrthosiphon pisum (pea aphids), mites, and Drosophila melanogaster (fruit flies). Myristicin was shown to be an effective repellent, and to cause mortality via direct and systemic exposure. It also displayed a synergistic effect when administered to insects in combination with existing insecticides.<ref name="Lichtenstein_1963" />
The chemical structure of myristicin is similar to some amphetamine compounds, and it may be capable of producing psychotropic effects.<ref name=Hallström/> Normal levels of intake of myristicin from spices in food is unlikely to cause these effects.<ref name=Hallström/> Myristicin can be used in the chemical synthesis of amphetamine derivatives such as the designer drug MMDMA that is 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/>
Furthermore, myristicin interferes with multiple signaling pathways and enzyme processes in the body.<ref name=pubchem/><ref name="Lee_2005" /><ref name="Yang_2015" />
Sources of myristicinEdit
Myristicin can be found in the essential oil of nutmeg, black pepper, kawakawa,<ref name="MeaningTrees">Template:Cite q</ref> and many members of the Umbelliferae family, including anise, carrots, parsley, celery, dill,<ref name="Rahman_2015">Template:Cite journal</ref> and parsnip.<ref name="Lichtenstein_1963" />
Trace amounts have also been isolated from a variety of plant species including Ridolfia segetum (harvest fennel), species of the Oenanthe genus (water dropworts), species of the Lamiaceae family (mint, sage, or deadnettle families), Cinnamomum glanduliferum (Nepal camphor tree),<ref>Template:Cite journal</ref> and Piper mullesua ("Hill Pepper").<ref name="Srivastava_2001">Template:Cite journal</ref>
Depending on the conditions of growth and storage of the plant, a high quality nutmeg (Myristica fragrans) seed can contain up to 13 mg of myristicin per 1 gram.<ref>Template:Cite journal</ref>
Physiological effectsEdit
Psychoactive effectsEdit
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 deliriants due to its hallucinogenic effects.<ref name=pubchem/><ref>Template:Cite journal</ref>
PharmacologyEdit
Myristicin is additionally known to be a weak inhibitor of monoamine oxidase (MAO), an enzyme in humans that metabolizes neurotransmitters (for example, serotonin, dopamine, epinephrine, and norepinephrine). It lacks the basic nitrogen atom that is typical of monoamine oxidase inhibitors (MAOIs), potentially explaining a weaker inhibitory effect.<ref>Template:Cite journal</ref>
While smaller concentrations of MAOIs may not cause problems, there are additional warnings regarding drug interactions. Those taking antidepressants that are MAOIs (such as phenelzine, isocarboxazid, tranylcypromine or selegiline<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>) or taking selective serotonin reuptake inhibiting (SSRI) antidepressants should avoid essential oils rich in myristicin, such as that of nutmeg and anise.<ref>Template:Cite book</ref>
MetabolitesEdit
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 transformed into demethylenylmyristicin, dihydroxymyristicin, and elemicin is transformed into O-demethylelemicin, O-demethyldihydroxyelemicin, and safrole.<ref name=pubchem/>Template:Cn
There has been speculation that myristicin might be converted into the psychedelic MMDA, but this has not been demonstrated in humans.<ref name="PiHKAL">Template:CitePiHKAL</ref><ref name="Al-RawiIbrahimAhmed2024">Template:Cite journal</ref><ref name="BraunKalbhen1973">Template:Cite journal</ref><ref name="BeyerEhlersMaurer2006">Template:Cite journal</ref> However, two nitrogen-containing metabolites of myristicin have been identified in the urine of rats and guinea pigs following oral or intraperitoneal administration. The major basic ninhydrin-positive urinary metabolite of myristicin in the rat is 3-piperidyl-1-(3′methoxy-4′,5′-methylenedioxyphenyl)-1-propanone, while the major basic ninhydrin-positive urinary metabolite of the guinea pig is 3-pyrrolidinyl-1-(3′methoxy-4′,5′-methylenedioxyphenyl)-1-propanone.<ref name="Oswald1971">Template:Cite journal</ref> Equivalent nitrogen-containing metabolites have also been identified for safrole<ref name="Oswald1971.safrole">Template:Cite journal</ref> and elemicin,<ref name="Oswald1971.elemicin">Template:Cite journal</ref> including the dimethylamine, piperidine and pyrrolidine forms.
ChemistryEdit
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 ethanol, ether, and benzene.<ref name=pubchem/>
ToxicityEdit
In laboratory studies, myristicin is cytotoxic. Specifically, it stimulates cytochrome c release, which activates caspase cascades and induces early apoptosis in the cells.<ref name="Lee_2005"/> Myristicin has also been shown to inhibit cytochrome P450 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 central nervous system leading to euphoria.<ref name=pubchem/><ref name=drugs/> Also occurring are mild to intense hallucinations (similar to those induced by deliriants: walls and ceiling glitching or breathing), disorientation to time and surroundings, dissociation, feelings of levitation, loss of consciousness, tachycardia, weak pulse, anxiety, and hypertension.<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, mydriasis or miosis, hypotension, shock, and potentially death.<ref name=pubchem/><ref name=drugs/><ref name=Hallström/>
Myristicin poisoning can be detected by testing levels of myristicin in the blood.<ref>Template:Cite bookTemplate:Pn</ref> There are no known antidotes for myristicin poisoning, and treatment focuses on symptom management and potential sedation in cases of extreme delirium or aggravation.<ref name=pubchem/><ref name = "Demetriades_2005">Template:Cite journal</ref>
ReferencesEdit
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