Abstract：
:A review of the literature indicates that the absolute oral bioavailability of exogenous melatonin in humans or in preclinical animal models has not been adequately characterized; hence, this study was undertaken. Pharmacokinetics of melatonin was studied in rats, dogs, and monkeys following intravenous and oral administrations, and the absolute oral bioavailability of melatonin was calculated from the area under the plasma concentration-time curve. The apparent elimination half-life of melatonin following an intravenous dose of 3 mg/kg (5 mg/kg in rats) was 19.8, 18.6, and 34.2 minutes, respectively, in rats, dogs, and monkeys. The dose normalized oral bioavailability of melatonin following a 10 mg/kg oral dose was 53.5% in rats, while it was in excess of 100% in dogs and monkeys. Further, bioavailability of melatonin following a 10 mg/kg intraperitoneal administration in rats was 74.0%, suggesting the lack of substantial first-pass hepatic extraction of melatonin in rats. However, the oral bioavailability of melatonin in dogs decreased to 16.9% following a 1 mg/kg oral dose, indicating dose-dependent bioavailability in dogs. In vitro permeability studies with CACO-2 cells suggest that melatonin is likely to be well absorbed in humans. In vitro metabolism studies with fresh liver slices from rats as well as human donors were conducted to compare the initial rates of metabolism of melatonin between the two species and the results suggest that the intrinsic clearance of melatonin in humans may be lower than that in rats.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Yeleswaram K,McLaughlin LG,Knipe JO,Schabdach Ddoi
10.1111/j.1600-079x.1997.tb00302.xsubject
Has Abstractpub_date
1997-01-01 00:00:00pages
45-51issue
1eissn
0742-3098issn
1600-079Xjournal_volume
22pub_type
杂志文章abstract：:We tested whether combined melatonin (Mel) and exendin-4 (Ex4) treatment can better preserve glomerular structural integrity after ischemia-reperfusion (IR) injury compared with either alone. Adult male Sprague Dawley rats (n = 50) were equally divided into sham control (SC), IR, IR-Ex4 (10 μg/kg subcutaneously 30 min...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12273
更新日期：2015-11-01 00:00:00
abstract：:A physiologically based model of arousal dynamics is improved to incorporate the effects of the light spectrum on circadian phase resetting, melatonin suppression, and subjective sleepiness. To account for these nonvisual effects of light, melanopic irradiance replaces photopic illuminance that was used previously in ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12681
更新日期：2020-10-01 00:00:00
abstract：:Bisphenol A (BPA) has been reported to adversely affect the mammalian reproductive system in both sexes. However, the underlying mechanisms regarding how BPA disrupts the mammalian oocyte quality and how to prevent it have not been fully defined. Here, we document that BPA weakens oocyte quality by impairing both oocy...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12396
更新日期：2017-04-01 00:00:00
abstract：:In previous studies, we have shown that mitochondrial respiratory chain (MRC) activity is decreased in patients with nonalcoholic steatohepatitis and in ob/ob mice and that peroxynitrite plays a pathogenic role. The present study examined whether melatonin, a peroxynitrite scavenger, prevents: (i) the in vitro effects...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2011.00868.x
更新日期：2011-08-01 00:00:00
abstract：:Both autophagy and melatonin play important roles in plant development and stress response. However, the direct correlation between autophagy and melatonin as well as the underlying mechanism remains elusive in plants. In this study, we discovered that the expression of three autophagy-associated genes (MeATG8b, 8c, a...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12652
更新日期：2020-08-01 00:00:00
abstract：:In mammals, the suprachiasmatic nuclei (SCN) constitute the main circadian clock, receiving input from the retina which allows synchronization of endogenous biological rhythms with the daily light/dark cycle. Over the year, the SCN encodes photoperiodic variations through duration of melatonin secretion, with abundant...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12711
更新日期：2020-12-16 00:00:00
abstract：:Our objective was to suppress the daily surge of melatonin in serum of prepubertal dairy heifers by manipulating intensity of light (Experiment 1) and duration of exposure to light (Experiment 2). Heifers in Experiment 1 were exposed to either 12 hr of darkness (000 lux, control), or 400, 800, or 1,200 lux of light du...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1992.tb00046.x
更新日期：1992-05-01 00:00:00
abstract：:Melatonin is involved in the control of various physiological functions, such as sleep, cell growth and free radical scavenging. The ability of melatonin to behave as an antioxidant, together with the fact that the Alzheimer-related amyloid β-peptide (Aβ) triggers oxidative stress through hydroxyl radical-induced cell...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12260
更新日期：2015-10-01 00:00:00
abstract：:The effect on nocturnal melatonin secretion of acute administration of the indirectly acting serotonin (5-HT) receptor agonists d-fenfluramine (30 mg) and paroxetine (20 mg) and a partial 5-HT1A receptor agonist ipsapirone (20 mg) was investigated in healthy male volunteers and compared to a placebo condition. Each su...
journal_title：Journal of pineal research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1600-079x.1996.tb00271.x
更新日期：1996-09-01 00:00:00
abstract：:The ultrastructure of the pineal gland in the adult cat is described and compared with that of other mammals. Connective tissue spaces showed capillaries with nonfenestrated endothelia and numerous unmyelinated nerve fibers. In the proximal region of the gland, myelinated nerve fibers coming from the anterior commissu...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1995.tb00148.x
更新日期：1995-03-01 00:00:00
abstract：:Melatonin has shown particular promise as a neuroprotective agent to prevent motoneuron death in animal models of both amyotrophic lateral sclerosis (ALS) and spinal cord injuries (SCI). However, an understanding of the roles of endogenous melatonin receptors including MT1, MT2, and orphan G-protein receptor 50 (GPR50...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2012.01022.x
更新日期：2013-01-01 00:00:00
abstract：:Earlier studies showed that melatonin reduced the growth of 17-beta-estradiol (E(2))-induced rat pituitary prolactin-secreting tumor (prolactinoma) in vivo. The mechanisms of melatonin's inhibitory action on the prolactin-secreting tumor were further explored by investigating the in vitro effects of melatonin on the g...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2006.00403.x
更新日期：2007-03-01 00:00:00
abstract：:Carbon tetrachloride (CCl4) exerts its toxic effects by the generation of free radicals. In this study we investigated whether melatonin, a potent free radical scavenger, could prevent the deleterious effects of CCl4. Liver homogenates and liver microsomes were incubated with CCl4 in the presence of melatonin and lipi...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1995.tb00164.x
更新日期：1995-08-01 00:00:00
abstract：:Lower global cognitive function scores are a common symptom of autism spectrum disorders (ASDs). This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescue...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12081
更新日期：2014-01-01 00:00:00
abstract：:The effects of melatonin (3 mg/kg i.p.) and the melatonin receptor agonist S-20098 (3 mg/kg i.p.) on the vigilance states, electroencephalogram power spectra (0.25-25.0 Hz), and cortical temperature were determined in eight rats in the first 6-hr interval of the 12-hr light period. Compared to the vehicle injection bo...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1994.tb00078.x
更新日期：1994-01-01 00:00:00
abstract：:An interaction between melatonin and adrenocorticotropin (ACTH) seems to occur in humans and both hormones respond to beta-adrenergic stimulation. As in lower animal species, human pineal gland also contains alpha2-adrenergic receptors as does the hypothalamus-pituitary axis. In this study the response of the pineal g...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2000.290107.x
更新日期：2000-08-01 00:00:00
abstract：:Melatonin has been shown to have a direct inhibitory action on the proliferation of estrogen-responsive MCF-7 human breast cancer cells in culture. In the present study, we examined by flow cytometry whether this inhibitory effect might be exerted on the G1 phase of the cell cycle, thus causing a transition delay into...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1991.tb00007.x
更新日期：1991-01-01 00:00:00
abstract：:The purpose of this study was to determine and compare the effects of chronic melatonin treatment in vivo on several aspects of prolactin (PRL) cell activity (PRL synthesis, storage, and release) in vitro in male and female Syrian hamsters. Adult male and female hamsters were maintained on long photoperiod and treated...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1989.tb00446.x
更新日期：1989-01-01 00:00:00
abstract：:The antioxidant and anti-inflammatory effects of melatonin on kainic acid (KA)-induced neurodegeneration in the hippocampus were evaluated in vivo. It has been suggested that the pineal secretory product, melatonin, protects neurons in vitro from excitotoxicity mediated by kainate-sensitive glutamate receptors, and fr...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2003.00010.x
更新日期：2003-03-01 00:00:00
abstract：:The rod outer segment (ROSg) membranes are essentially lipoprotein complexes. Rhodopsin, the major integral protein of ROSg, is surrounded by phospholipids highly enriched in docosahexaenoic acid (22:6 n3). This fluid environment plays an important role for conformational changes after photo-activation. Thus, ROSg mem...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2006.00352.x
更新日期：2006-10-01 00:00:00
abstract：:Melatonin, which is contained in certain vegetables, may have an influence on circulatory melatonin concentrations. This study examined the effects of the consumption of vegetables on 6-sulfatoxymelatonin concentrations in morning urine. Ninety-four healthy women aged 24-55 were recruited through a city public health ...
journal_title：Journal of pineal research
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1600-079X.2007.00549.x
更新日期：2008-08-01 00:00:00
abstract：:Melatonin regulates mitogen-activated protein kinase (MAPK) and Akt signaling pathways. The MAPK family mainly includes extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Our previous study documented that melatonin delays osteoblast proliferation; however, the mechanism of action of ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2011.00971.x
更新日期：2012-08-01 00:00:00
abstract：:Melatonin is a highly effective treatment in different animal models of excitotoxicity or ischemia/reperfusion injury. Due to a lack of patentability, commercial sponsors are not interested in funding clinical evaluations of melatonin. Investigators may initiate small-scale clinical evaluation, and intravenous (i.v.) ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2006.00372.x
更新日期：2006-11-01 00:00:00
abstract：:We tested the hypothesis that melatonin (Mel) enhances exogenous mitochondria (Mito) treatment against rodent hepatic ischemia-reperfusion (IR) injury. In vitro study utilized three groups of hepatocytes (i.e. nontreatment, menadione, and menadione-melatonin treatment, 4.0 × 10(5) each), while in vivo study used adult...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12326
更新日期：2016-08-01 00:00:00
abstract：:The pineal gland of poikilothermic vertebrates originates as an evagination from the diencephalic roof between the habenular and the posterior commissures, and associates with a parapineal organ to form the so-called pineal complex. The pinealocytes may be photosensitive, secretory or intermediate cells between both. ...
journal_title：Journal of pineal research
pub_type： 杂志文章,评审
doi：10.1111/j.1600-079x.1996.tb00256.x
更新日期：1996-05-01 00:00:00
abstract：:The influence of the pineal gland on the histopathologic changes induced in mammary glands by 7, 12-dimethylbenz(a)-anthracene (DMBA) has been studied. To achieve the maximum expression of pineal action in animals, 28-day-old female Sprague-Dawley rats were subjected to one of the following treatments: blindness + olf...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1989.tb00418.x
更新日期：1989-01-01 00:00:00
abstract：:Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preeclampsia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine whether melatonin could be a useful adjuvant therapy. In a xanthine/x...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12508
更新日期：2018-10-01 00:00:00
abstract：:Melatonin injected in a single intraperitoneal dose of 100 micrograms/100 g b.w. to euhydrated rats resulted in a decrease of neurohypophysial oxytocin content but the hypothalamic oxytocin storage as well as the hypothalamo-neurohypophysial storage of vasopressin were not changed. Following 8 d of once-daily melatoni...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1986.tb00743.x
更新日期：1986-01-01 00:00:00
abstract：:GPR50 is an orphan seven transmembrane protein related to the melatonin receptor subfamily comprising MT(1) and MT(2) receptors. In the absence of any known ligand for GPR50, other tools are critical for the characterization of this protein. Here, we describe the generation, purification and characterization of the fi...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00437.x
更新日期：2007-08-01 00:00:00
abstract：:In a recent study melatonin (N-acetyl-5-methoxytryptamine), a well-investigated animal molecule but minimally studied in plants, was seen to have a physiological role as growth-promoting molecule in lupin hypocotyls. In the present study, the role of melatonin as a growth promoter is extended to coleoptiles of canary ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2005.00226.x
更新日期：2005-09-01 00:00:00
