Melatonin interactions

Niles, L. (1991). Melatonin interaction with the benzodiazepine-GABA receptor complex in the CNS. Adv. Exp. Med. Biol. 294, 267-77. 

Recent studies in a model of ischemic stroke suggest that the acute neuro-protective effect of melatonin involves activation of the phosphatidylinositol-3-kinase/Akt pathway, whereas ERK-1/2 and c-Jun N-terminal kinase-1/2, in addition to Akt signaling, appear to be involved in its long-term effects (Kilic et al. 2005). These results indicate that melatonin can interact with multiple cellular pathways to produce its diverse physiological effects. Moreover, MTi and MT2 receptors can interact with divergent signaling pathways, as shown by their ability to... 

In addition to its interaction with central BZD receptors, pharmacological concentrations of melatonin can also bind to the peripheral-type BZ receptors (PBRs), which are involved in neurosteroidogenesis (Garcia-Ovejero et al. 2005). PBRs are primarily localized on the outer mitochondrial membrane these sites are therefore also referred to as mitochondrial BZD receptors. Using the isoquinoline carboxamide, PK14105, for photoaffinity labelling, an 18 kDa isoquinoline... 

Golombek, D. A, Martini, M. 8r Cardinali, D. P. (1993). Melatonin as an anxiolytic in rats time-dependence and interaction with the central gabaergic system. Eur. J. Pharmacol. 237, 231-6. 

There was an increase in blood pressure throughout 24 hours in a double-bhnd, placebo-controlled, crossover study in 47 hypertensive patients who were also taking nifedipine (10). This finding differs from other studies in which melatonin had a mild hypotensive effect (11) and may indicate an interaction between melatonin and nifedipine. Tachycardia, chest pain, and cardiac dysrhythmias have also been reported, although the relation to melatonin was not clearly established (5). 

Melatonin affects reproduction in seasonally breeding animals. In humans, findings of increased endogenous melatonin in hypogonadism and low concentrations in precocious puberty imply an interaction between melatonin and gonadotropins however, data on the effects of exogenous melatonin are limited (1). In a randomized study in 16 women, melatonin enhanced LH and FSH responses to submaximal GnRH stimuli in the follicular but not the luteal phase of the menstrual cycle (24). 

Melatonin overdose has been reported in three patients, all of whom were also taking psychotropic drugs. Drug interactions with antidepressants may have played a part in the resulting symptoms, which were not reported in cancer trials using higher doses of melatonin (1). 

While many commercially available preparations contain only melatonin, many others contain a combination of this hormone with other active ingredients. Some of these other ingredients may be vitamins such as pyri-doxine, while others are natural remedies such as kava root and valerian. It is even available combined with acetaminophen, a common over-the-counter pain reliever. Frequently, the long-term effects and safety of these other ingredients are not known. Even less is known about any possible interactions between these substances and melatonin, because melatonin has been available and used commercially for only a short period of time. Many experts have suggested that it would be preferable to test melatonin in controlled studies to determine if it is effective and safe before it was released on the market and used by millions of people. 

Much remains unknown about melatonin s interaction with many other drugs and substances. However, it is known that melatonin does interact with, and may limit the effectiveness of, benzodiazepines, methamphetamines, dehydroepiandrosterone, magnesium, zinc, corticosteroids, and succinylcholine. People who are being treated with these drugs should not take melatonin. 

Interactions between drugs or substances and endogenous melatonin... 

The long-term personal and social consequences of routinely using melatonin are not known. It is known, however, that millions of people take over-the-counter melatonin preparations containing very large doses of melatonin relative to the amount produced by the human body or contained in foods. Even less is known about its interaction with other drugs or natural remedies. Many experts are concerned that such large-scale use of a hormone may not be safe. Serious health implications of using melatonin may not be discovered until many people have placed themselves at risk. 

Melatonin drug interactions have not been formally studied. Various studies, however, suggest that melatonin concentrations are altered by a variety of drugs, including NSAIDs, antidepressants, B-... 

Melatonin oxidation seems quite important for the production of other biologically active metabolites such as AFMK and A -acetyl-S-methoxykynur-amine (AMK). AMK interacts with reactive oxygen and nitrogen species, conveys protection to mitochondria, inhibits and downregulates COX-2. Thus, melatonin may be considered as a prodrug [61]. 

The mechanism of melatonin s interaction with reactive species probably involves donation of an electron to form the melatoninyl cation radical or through a radical addition at the site C3. Other possibilities include hydrogen donation from the nitrogen atom or substitution at position C2, C4, and C7 and nitrosation [169]. The mechanisms by which melatonin protects against LP most likely involve direct or indirect antioxidant and free-radical scavenging activities of this indoleamine [169,171]. 2-Phenyl indole derivatives have redox properties because of the presence of an electron-rich aromatic ring system that allows the indoleamine to easily function as an electron donor. For these derivatives, the possible antioxidant mechanism might be most probably toward carbon-centered radicals described by Antosiewicz et al. [172]. 

Melatonin is an indole-derived anterior pituitary hormone that causes downstream inhibition of a-MSH-induced melanogenesis. Melatonin is antiamnesic, synchronizes circadian and circannual rhythms and is metabolized to 5-methoxytryptamine. Melatonin acts via GPCRs MT1 and MT2 (which both couple through Gai and cAMP decrease). MT1 may also couple via Gao and Gaq to activate PLC (and hence increase cytosolic Ca2+) and via G Gy activation of PLA2. Melatonin can further interact with nuclear receptor superfamily orphan retinoid receptors RZR/ROR. Melatonin fluctuates with a circadian rhythm and is elevated in blood during the night. Melatonin is accordingly of social importance in relation to shift work and jet-lag. Melatonin and 5-methoxytryptamine occur in some plants (Table 5.8). 

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