Over-the-Counter Psychotropics: A Review of Melatonin, St John's Wort, Valerian, and Kava-Kava

Heiligenstein, Eric; Guenther, Greta

doi:10.1080/07448489809596003

Cited by 24 publications

(17 citation statements)

References 21 publications

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“…MEL has been evaluated as a therapeutic agent in a number of conditions, including sleep disturbance, jet lag, and metastatic cancer (Lissoni et al, 1989;Herxheimer and Petrie, 2002;Singer et al, 2003). These putative pleiotropic effects of MEL have not gone unnoticed by the dietary supplement industry: MEL is sold unregulated as a dietary supplement, and some concerns have been expressed regarding potential toxicity and drug interactions (Holliman and Chyka, 1997;Heiligenstein and Guenther, 1998). One prominent internet vendor lists 102 melatonin products under 32 separate brand names and mentions MEL in relation to such diverse conditions as jet lag, cluster headaches, lung cancer, depression, glaucoma, and epilepsy.…”

mentioning

confidence: 99%

Metabolism of Melatonin by Human Cytochromes P450

Ma¹,

Idle²,

Krausz³

et al. 2004

Drug Metab Dispos

289

231

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ABSTRACT:In humans, the pineal hormone melatonin (MEL) is principally metabolized to 6-hydroxymelatonin (6-HMEL), which is further conjugated with sulfate and excreted in urine. MEL O-demethylation represents a minor reaction. The exact role of individual human cytochromes P450 (P450s) in these pathways has not been established. We used a panel of 11 recombinant human P450 isozymes to investigate for the first time the 6-hydroxylation and O-demethylation of MEL. CYP1A1, CYP1A2, and CYP1B1 all 6-hydroxylated MEL, with CYP2C19 playing a minor role. These reactions were NADPH-dependent. CYP2C19 and, to some extent CYP1A2, Odemethylated MEL. The K m (M) and V max (k cat , pmol min ؊1 pmol ؊1 P450) for 6-hydroxylation were estimated as 19.2 ؎ 2.01 and 6.46 ؎ 0.22 (CYP1A1), 25.9 ؎ 2.47 and 10.6 ؎ 0.32 (CYP1A2), and 30.9 ؎ 3.76 and 5.31 ؎ 0.21 (CYP1B1). These findings confirm the suggestion of others that CYP1A2 is probably the foremost hepatic P450 in the 6-hydroxylation of MEL and a single report that CYP1A1 is also able to mediate this reaction. However, this is the first time that CYP1B1 has been shown to 6-hydroxylate MEL. The IC 50 for the CYP1B1-selective inhibitor (E)-2,4,3,5-tetramethoxystilbene was estimated to be 30 nM for MEL 6-hydroxylation by recombinant human CYP1B1. Comparison of brain homogenates from wild-type and cyp1b1-null mice revealed that MEL 6-hydroxylation was clearly mediated to a significant degree by CYP1B1. CYP1B1 is not expressed in the liver but has a ubiquitous extrahepatic distribution, and is found at high levels in tissues that also accumulate either MEL or 6-HMEL, such as intestine and cerebral cortex, where it may assist in regulating levels of MEL and 6-HMEL.

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mentioning

confidence: 99%

Metabolism of Melatonin by Human Cytochromes P450

Ma¹,

Idle²,

Krausz³

et al. 2004

Drug Metab Dispos

289

231

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“…That a product is "natural" does not mean that it is either safe or effective. Many supplements are potent drugs that lack sufficient data on safety, doseresponse relationships, drug interactions, and purity 247 . It has been reported that melatonin consumption has resulted in eosinophilia in some humans taking high doses of this supplement.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2013

IJPSR

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ABSTRACT:Introduction: Melatonin is a neuro-hormone secreted from the pineal gland and involved in various regulatory activities in body. Ever-increasing use of melatonin supplements and enlarging research evidences make the authors undertook the review to arrive at a qualitative conclusion whether melatonin supplements can act as potential treatment options or not. Methodology: A comprehensive search was undertaken in different electronic databases using various search terms. A total of 225 studies were identified including clinical research studies and basic experiments. Data were extracted individually from the studies and compiled in the end. Results: Melatonin has been used successfully in chronic insomnia and as an anti-oxidant in cancer and other age-related neuro-degenerative disorders, especially Alzheimer's disease and Autistic disorders. Its evidences of use in other conditions remained insufficient and inconclusive. Conclusion: Melatonin therapy may be considered as efficacious and safe in insomnia and as an anti-oxidant; however, other roles needs to be evaluated in further studies.

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“…The concentration of melatonin in the digestive mucosa typically exceeds that found in the blood, by up to 100 times . In most countries, including the United States of America (USA), melatonin is easily available as an over‐the‐counter oral supplement …”

Section: What Is Known and Objectivementioning

confidence: 99%

Agomelatine, a novel therapeutic option for the management of irritable bowel syndrome

Soh

Lim

et al. 2018

J Clin Pharm Ther

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Summary What is known and objective Irritable bowel syndrome (IBS) is a complex and chronic, relapsing gastrointestinal condition that affects more than 10% of the population worldwide. There is a pressing need for new therapeutic strategies in the management of IBS. Increasing research has shed light on the modulatory functions of melatonin on pain, local inflammation and motility in the gastrointestinal tract. However, melatonin's effects are limited by its extensive first‐pass metabolism and short half‐life. Comment Agomelatine, a naphthalene analog of melatonin, is a novel melatonergic drug with a longer half‐life and a comparatively greater affinity for MT1 and MT2 melatonin receptors than melatonin itself. Agomelatine also shows serotonin 5‐HT3 receptor antagonist activity, which is theoretically of benefit for patients with IBS with diarrhoea (IBS‐D) as it regulates gastrointestinal motility and visceral sensory mechanisms. Although only one clinical study of agomelatine use in patients with IBS exists, we believe that agomelatine is a safe and efficacious multimodal agent with untapped potential in the management of IBS. What is new and conclusion Numerous comorbidities are associated with IBS, including chronic pain syndromes and psychiatric disorders. Coupled with its antidepressant actions, agomelatine could serve as an effective adjunct therapeutic. Agomelatine should be considered in our therapeutic armamentarium for IBS management.

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Over-the-Counter Psychotropics: A Review of Melatonin, St John's Wort, Valerian, and Kava-Kava

Cited by 24 publications

References 21 publications

Metabolism of Melatonin by Human Cytochromes P450

Metabolism of Melatonin by Human Cytochromes P450

Untitled

Agomelatine, a novel therapeutic option for the management of irritable bowel syndrome

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