Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cows that could induce skin lightening in common frogs. This compound was later identified as a hormone secreted in the brain during the night, playing a crucial role in regulating the sleep-wake cycle, also known as the circadian rhythm, in vertebrates.
Phenelzine, sold under the brand name Nardil among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine family which is primarily used as an antidepressant and anxiolytic to treat depression and anxiety. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use.
Aniracetam, also known as N-anisoyl-2-pyrrolidinone, is a racetam which is sold in Europe as a prescription drug. It is not approved by the Food and Drug Administration for use in the United States as a prescription medication or dietary supplement. Despite the FDA's lack of approval, the drug is readily available over-the-counter in misbranded dietary supplements.
Sotolon is a butenolide lactone and an extremely potent aroma compound, with the typical smell of fenugreek or curry at high concentrations and maple syrup, caramel, or burnt sugar at lower concentrations. Sotolon is the major aroma and flavor component of fenugreek seed and lovage, and is one of several aromatic and flavor components of artificial maple syrup. It is also present in molasses, aged rum, aged sake and white wine, flor sherry, roast tobacco, and dried fruiting bodies of the mushroom Lactarius helvus. Sotolon can pass through the body relatively unchanged, and consumption of foods high in sotolon, such as fenugreek, can impart a maple syrup aroma to one's sweat and urine. In some individuals with the genetic disorder maple syrup urine disease, sotolon is spontaneously produced in their bodies and excreted in their urine, leading to the disease's characteristic smell.
Metaxalone, sold under the brand name Skelaxin, is a muscle relaxant medication used to relax muscles and relieve pain caused by strains, sprains, and other musculoskeletal conditions. Its exact mechanism of action is not known, but it may be due to general central nervous system depression. It is a moderately strong muscle relaxant, with relatively low incidence of side effects.
Zearalenone (ZEN), also known as RAL and F-2 mycotoxin, is a potent estrogenic metabolite produced by some Fusarium and Gibberella species. Specifically, the Gibberella zeae, the fungal species where zearalenone was initially detected, in its asexual/anamorph stage is known as Fusarium graminearum. Several Fusarium species produce toxic substances of considerable concern to livestock and poultry producers, namely deoxynivalenol, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and zearalenone. Particularly, ZEN is produced by Fusarium graminearum, Fusarium culmorum, Fusarium cerealis, Fusarium equiseti, Fusarium verticillioides, and Fusarium incarnatum. Zearalenone is the primary toxin that binds to estrogen receptors, causing infertility, abortion or other breeding problems, especially in swine. Often, ZEN is detected together with deoxynivalenol in contaminated samples and its toxicity needs to be considered in combination with the presence of other toxins.
Lercanidipine is an antihypertensive drug. It belongs to the dihydropyridine class of calcium channel blockers, which work by relaxing and opening the blood vessels allowing the blood to circulate more freely around the body. This lowers the blood pressure and allows the heart to work more efficiently.
Melatonin receptors are G protein-coupled receptors (GPCR) which bind melatonin. Three types of melatonin receptors have been cloned. The MT1 (or Mel1A or MTNR1A) and MT2 (or Mel1B or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype MT3 (or Mel1C or MTNR1C) has been identified in amphibia and birds. The receptors are crucial in the signal cascade of melatonin. In the field of chronobiology, melatonin has been found to be a key player in the synchrony of biological clocks. Melatonin secretion by the pineal gland has circadian rhythmicity regulated by the suprachiasmatic nucleus (SCN) found in the brain. The SCN functions as the timing regulator for melatonin; melatonin then follows a feedback loop to decrease SCN neuronal firing. The receptors MT1 and MT2 control this process. Melatonin receptors are found throughout the body in places such as the brain, the retina of the eye, the cardiovascular system, the liver and gallbladder, the colon, the skin, the kidneys, and many others. In 2019, X-ray crystal and cryo-EM structures of MT1 and MT2 were reported.
N-Acetylserotonin O-methyltransferase, also known as ASMT, is an enzyme which catalyzes the final reaction in melatonin biosynthesis: converting Normelatonin to melatonin. This reaction is embedded in the more general tryptophan metabolism pathway. The enzyme also catalyzes a second reaction in tryptophan metabolism: the conversion of 5-hydroxy-indoleacetate to 5-methoxy-indoleacetate. The other enzyme which catalyzes this reaction is n-acetylserotonin-o-methyltransferase-like-protein.
N-Acetylserotonin (NAS), also known as normelatonin, is a naturally occurring chemical intermediate in the endogenous production of melatonin from serotonin. It also has biological activity in its own right, including acting as a melatonin receptor agonist, an agonist of the TrkB, and having antioxidant effects.
Felinine, also known as (R)-2-amino-3-(4-hydroxy-2-methylbutan-2-ylthio)propanoic acid, is an amino acid found in cat urine and a precursor via microbial lyase of the putative cat pheromone and thiol called 3-mercapto-3-methylbutan-1-ol (MMB). Felinine is excreted by some Felidae species, including bobcats, Chinese desert cats, the kodkod, and domestic cats.
Lumirubin is a structural isomer of bilirubin, which is formed during phototherapy used to treat neonatal jaundice. This polar isomer resulting from the blue-green lights of phototherapy has an active site to albumin, and its effects are considered less toxic than those of bilirubin. Lumirubin is excreted into bile or urine. ZZ, ZE, EE and EZ are the four structural isomers of bilirubin. ZZ is the stable, more insoluble form. Other forms are relatively soluble and are known as lumirubins. Phototherapy converts the ZZ form into lumirubins. Monoglucuronylated lumirubins are easily excreted.
Pinoline is a methoxylated tryptoline (5-methoxytryptoline) long claimed to be produced in the pineal gland during the metabolism of melatonin, however its pineal occurrence remains controversial. Its IUPAC name is 6-methoxy-1,2,3,4-tetrahydro-β-carboline, usually abbreviated as 6-MeO-THBC, and its more common name is a combination of "pineal beta-carboline". The biological activity of this molecule is of interest as a potential free radical scavenger, also known as an antioxidant, and as a monoamine oxidase A inhibitor.
Saliva testing or Salivaomics is a diagnostic technique that involves laboratory analysis of saliva to identify markers of endocrine, immunologic, inflammatory, infectious, and other types of conditions. Saliva is a useful biological fluid for assaying steroid hormones such as cortisol, genetic material like RNA, proteins such as enzymes and antibodies, and a variety of other substances, including natural metabolites, including saliva nitrite, a biomarker for nitric oxide status. Saliva testing is used to screen for or diagnose numerous conditions and disease states, including Cushing's disease, anovulation, HIV, cancer, parasites, hypogonadism, and allergies. Salivary testing has even been used by the U.S. government to assess circadian rhythm shifts in astronauts before flight and to evaluate hormonal profiles of soldiers undergoing military survival training.
Hydroxybupropion, or 6-hydroxybupropion, is the major active metabolite of the antidepressant and smoking cessation drug bupropion. It is formed from bupropion by the liver enzyme CYP2B6 during first-pass metabolism. With oral bupropion treatment, hydroxybupropion is present in plasma at area under the curve concentrations that are as many as 16 to 20 times greater than those of bupropion itself, demonstrating extensive conversion of bupropion into hydroxybupropion in humans. As such, hydroxybupropion is likely to play a very important role in the effects of oral bupropion, which could accurately be thought of as functioning largely as a prodrug to hydroxybupropion.
6β-Hydroxycortisol is an endogenous steroid. In humans, it is a metabolite of cortisol produced by cytochrome p450-3A monooxygenases, mainly, 6β-hydroxysteroid dehydrogenase (CYP3A4). 6β-hydroxycortisol is used as a biomarker of 6β-hydroxysteroid dehydrogenase (CYP3A4) activity. Drugs that induce CYP3A4 may accelerate cortisol clearance, by accelerating cortisol conversion to 6β-hydroxycortisol, and vice versa: drugs that inhibit CYP3A4 can slow down cortisol clearance, as they reduce the conversion of cortisol to 6β-hydroxycortisol.
Desmethylsibutramine is an active metabolite of the anorectic drug sibutramine. It is a more potent monoamine reuptake inhibitor than sibutramine and has been sold as an ingredient in weight loss products sold as dietary supplements, along with related compounds such as the N-ethyl and 3,4-dichloro derivatives.
Melatonin is a naturally occurring hormone produced in the brain that is also used as a dietary supplement and medication. As a hormone, melatonin is released by the pineal gland and is involved in sleep–wake cycles. As a supplement, it is often used for the attempted short-term treatment of disrupted sleep patterns, such as from jet lag or shift work, and is typically taken orally. There is evidence of its benefit for this use, but is not strong. A 2017 review found that sleep onset occurred six minutes faster with use on average, but found no change in total time asleep.
Chlorosibutramine is an analogue of the anorectic drug sibutramine, which has been sold as an ingredient in weight loss products sold as dietary supplements, first detected in South Korea in 2013. It is illegal in South Korea.
Cyclic 3-hydroxymelatonin (3-OHM) is a metabolite of melatonin and an antioxidant more potent than melatonin. It is a non-radical species and does not further propagate the radical chain reaction
