Effects of Melatonin on Sleep and Neurochemistry in the Rat

Holmes, S. W.; Sugden, David

doi:10.1111/j.1476-5381.1982.tb09194.x

Cited by 86 publications

(38 citation statements)

References 21 publications

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“…The doses used in the study show a comparable effect as the therapeutic dosages. Therefore, although melatonin is an effective hypnotic agent both in animals (17,18) and humans (19), these findings suggest that melatonin may not directly affect the hypnotic action of zaleplon.…”

Section: Discussionmentioning

confidence: 93%

Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Noguchi¹,

Kitazumi²,

Mori³

et al. 2003

J Pharmacol Sci

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Abstract. Melatonin, a major hormone secreted by the pineal gland, is known to play an important role in regulation of the circadian rhythm. (N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide (zaleplon) is a non-benzodiazepine hypnotic that acts via the benzodiazepine site of the GABA A receptor. In the present study, we investigated the effect of zaleplon on melatonin secretion in rabbits using RIA and compared the effect to triazolam and zopiclone. Zaleplon increased a dose-dependent concentration of melatonin in rabbit plasma collected at 30 min after intravenous administration at doses of 1 and 2 mg / kg. The zaleploninduced increase in plasma melatonin level was not blocked by flumazenil, a benzodiazepinereceptor antagonist. In contrast, triazolam and zopiclone failed to affect the plasma melatonin level. We also investigated the effect of zaleplon on intracellular cAMP in rat pinealocytes. Consequently, zaleplon had no effect on the intracellular cAMP levels in rat pinealocytes. These results of the present studies suggest that zaleplon may promote melatonin secretion and the elevation of plasma levels of melatonin may suggest an influence of zaleplon on chronobiology.

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Section: Discussionmentioning

confidence: 93%

Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Noguchi¹,

Kitazumi²,

Mori³

et al. 2003

J Pharmacol Sci

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“…Animal studies have demonstrated that MLT reduces time to sleep onset and increases both NREMS and REMS (Holmes and Sugden, 1982;Mirmiran and Pevet, 1986), with both effects being blocked by the GABA A receptor antagonists flumazenil and picrotoxin (Wang et al, 2003a). Other studies showed little or no effect (Mailliet et al, 2001;Wang et al, 2003b).…”

Section: Introductionmentioning

confidence: 99%

Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT₂Melatonin Receptor Ligand

Ochoa‐Sanchez¹,

Comai²,

Lacoste³

et al. 2011

J. Neurosci.

113

127

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“…Holmes and Sugden 65 reported that MLT reduces time to sleep onset and increases both SWS and PS. Others suggest that MLT is involved only in the control of PS regulation since the lesion of the pineal gland or inhibition of MLT synthesis using a β-adrenergic antagonist (propranolol) decreased PS during light and dark periods.…”

Section: Melatonin and Sleepmentioning

confidence: 99%

Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology

Comai

Gobbi

2014

J Psychiatry Neurosci

153

126

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IntroductionMelatonin (MLT) is a neurohormone synthesized from serotonin (5-HT) and secreted foremost by the mammalian pineal gland following a distinct circadian rhythm with the acrophase during the dark phase and the nadir during the light phase in both diurnal and nocturnal species.1 A typical human adult's average daytime and nighttime levels of blood MLT are approximately 10 pg/mL and 60 pg/mL, respectively.2 Its production is controlled through the suprachiasmatic nucleus (SCN) by the photoperiod, peaking at night and dropping during the day. Melatonin is involved in numerous physiologic processes, including circadian rhythms, mood regulation, anxiety, sleep, appetite, immune responses and cardiac functions. 3,4 Most of the effects of MLT in the brain result from the activation of 2 high-affinity G-protein coupled receptors (GPCRs), MT 1 and MT 2 .5 Of note, GPCRs have a proven history of being excellent therapeutic targets. Recent market analyses indicate that 40%-50% of modern drugs and almost 25% of the top 200 best-selling drugs target GPCRs. 6 In addition to these high-affinity MLT receptors, another low-affinity MLT binding site, MT 3 , has recently been characterized as an MLT-sensitive form of the human enzyme quinone reductase 2. 7 The functional characterization of MT 1 and MT 2 receptors in target tissues is hampered by the paucity of selective MT 1 and MT 2 receptor ligands. Structural Background: Melatonin (MLT) is a pleiotropic neurohormone controlling many physiological processes and whose dysfunction may contribute to several different diseases, such as neurodegenerative diseases, circadian and mood disorders, insomnia, type 2 diabetes and pain. Melatonin is synthesized by the pineal gland during the night and acts through 2 G-protein coupled receptors (GPCRs), MT 1 (MEL1a) and MT 2 (MEL1b). Although a bulk of research has examined the physiopathological effects of MLT, few studies have investigated the selective role played by MT 1 and MT 2 receptors. Here we have reviewed current knowledge about the implications of MT 2 receptors in brain functions. Methods: We searched PubMed, Web of Science, Scopus, Google Scholar and articles reference lists for studies on MT 2 receptor ligands in sleep, anxiety, neuropsychiatric diseases and psychopharmacology, including genetic studies on the MTNR1B gene, which encodes the melatonin MT 2 receptor. Results: These studies demonstrate that MT 2 receptors are involved in the pathophysiology and pharmacology of sleep disorders, anxiety, depression, Alzheimer disease and pain and that selective MT 2 receptor agonists show hypnotic and anxiolytic properties. Limitations: Studies examining the role of MT 2 receptors in psychopharmacology are still limited. Conclusion: The development of novel selective MT 2 receptor ligands, together with further preclinical in vivo studies, may clarify the role of this receptor in brain function and psychopharmacology. The superfamily of GPCRs has proven to be among the most successful drug targets and, consequently, M...

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Effects of Melatonin on Sleep and Neurochemistry in the Rat

Cited by 86 publications

References 21 publications

Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT₂Melatonin Receptor Ligand

Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology

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Effects of Melatonin on Sleep and Neurochemistry in the Rat

Cited by 86 publications

References 21 publications

Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT2Melatonin Receptor Ligand

Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology

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Product

Resources

About

Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT₂Melatonin Receptor Ligand