Melatonin receptors: molecular pharmacology and signalling in the context of system bias

British Journal of Pharmacology, Journal Year: 2017, Volume and Issue: 175(16), P. 3263 - 3280

Published: July 14, 2017

Melatonin, N ‐acetyl‐5‐methoxytryptamine, an evolutionally old molecule, is produced by the pineal gland in vertebrates, and it binds with high affinity to melatonin receptors, which are members of GPCR family. Among multiple effects attributed melatonin, we will focus here on those that dependent activation two mammalian MT 1 2 receptors. We briefly summarize latest developments synthetic receptor ligands, including multi‐target‐directed characterization signalling‐biased ligands. discuss signalling pathways activated receptors appear be highly cell‐ tissue‐dependent, emphasizing impact system bias functional outcome. Different proteins have been demonstrated interact thus, postulate part this has its molecular basis differences expression receptor‐associated heterodimerization partners. Finally, at level receptor, genetic variants, discussed show how a modified function can effect risk for common diseases like type diabetes humans. Linked Articles This article themed section Recent Developments Research Melatonin Potential Therapeutic Applications. To view other articles visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc

Language: Английский

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Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders

Pharmacology & Therapeutics, Journal Year: 2019, Volume and Issue: 204, P. 107402 - 107402

Published: Aug. 27, 2019

Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need improved drug treatments. In this review an overview drugs being studied different phases clinical trials their potential treatment fear-, anxiety- trauma-related presented. One strategy followed development refining improving compounds interacting with existing anxiolytic targets, such as serotonergic prototypical GABAergic benzodiazepines. A more innovative approach involves search novel mechanisms action using growing knowledge base concerning relevant neurocircuitries neurobiological underlying pathological fear anxiety. The target systems evaluated include glutamate, endocannabinoid neuropeptide systems, well ion channels targets derived from phytochemicals. Examples promising candidates currently generalised disorder, social panic obsessive compulsive disorder or post-traumatic stress ketamine, riluzole, xenon one common pharmacological modulation glutamatergic neurotransmission, neurosteroid aloradine. Finally, D-cycloserine, MDMA, L-DOPA cannabinoids have shown efficacy enhancing fear-extinction learning humans. They are thus investigated augmentative speeding up long-term effectiveness exposure-based psychotherapy, which could render chronic dispensable many patients. These efforts indicative a rekindled interest renewed optimism discovery field, after decades relative stagnation.

Language: Английский

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Circadian Rhythm Disturbances in Mood Disorders: Insights into the Role of the Suprachiasmatic Nucleus

Neural Plasticity, Journal Year: 2017, Volume and Issue: 2017, P. 1 - 28

Published: Jan. 1, 2017

Circadian rhythm disturbances are a common symptom among individuals with mood disorders. The suprachiasmatic nucleus (SCN), in the ventral part of anterior hypothalamus, orchestrates physiological and behavioral circadian rhythms. SCN consists self-sustaining oscillators receives photic nonphotic cues, which entrain to external environment. In turn, through synaptic hormonal mechanisms, can drive synchronize rhythms extra-SCN brain regions peripheral tissues. Thus, genetic or environmental perturbations could disrupt more closely related regulation cause disturbances. Here, we review clinical preclinical studies that provide evidence both for against causal role

Language: Английский

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Molecular targets of atypical antipsychotics: From mechanism of action to clinical differences

Pharmacology & Therapeutics, Journal Year: 2018, Volume and Issue: 192, P. 20 - 41

Published: June 25, 2018

Language: Английский

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Structural basis of ligand recognition at the human MT1 melatonin receptor

Nature, Journal Year: 2019, Volume and Issue: 569(7755), P. 284 - 288

Published: April 24, 2019

Language: Английский

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Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

European Neuropsychopharmacology, Journal Year: 2015, Volume and Issue: 25(5), P. 599 - 656

Published: Feb. 7, 2015

Language: Английский

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Chronobesity: role of the circadian system in the obesity epidemic

Obesity Reviews, Journal Year: 2015, Volume and Issue: 17(2), P. 108 - 125

Published: Dec. 23, 2015

Summary Although obesity is considered to result from an imbalance between energy uptake and expenditure, the strategy of dietary changes physical exercise has failed tackle global epidemic. In search alternative more adequate treatment options, research aimed at further unravelling mechanisms underlying this excessive weight gain. While numerous studies are focusing on neuroendocrine alterations that occur after bariatric Roux‐en‐Y gastric bypass surgery, increasing amount chronobiological have started raise awareness concerning pivotal role circadian system in development exacerbation obesity. This internal timekeeping mechanism rhythmically regulates metabolic physiological processes order meet fluctuating demands use supply throughout 24‐h day. review elaborates extensive bidirectional interaction metabolism explains how disruption body clocks by means shift work, frequent time zone travelling or non‐stop consumption calorie‐dense foods can evoke detrimental contribute Altering body's rhythms time‐related approaches (chrononutrition) pharmacological substances (chronobiotics) may therefore represent a novel interesting way prevent treat associated comorbidities.

Language: Английский

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Molecular aspects of depression: A review from neurobiology to treatment

European Journal of Pharmacology, Journal Year: 2019, Volume and Issue: 851, P. 99 - 121

Published: Feb. 15, 2019

Language: Английский

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New therapeutic opportunities for 5-HT2C receptor ligands in neuropsychiatric disorders

Pharmacology & Therapeutics, Journal Year: 2015, Volume and Issue: 157, P. 125 - 162

Published: Nov. 23, 2015

Language: Английский

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Clinical management of sleep disturbances in Alzheimer's disease: current and emerging strategies

Nature and Science of Sleep, Journal Year: 2016, Volume and Issue: unknown, P. 21 - 21

Published: Jan. 1, 2016

Abstract: Sleep and circadian disorders in Alzheimer's disease (AD) are more frequent than the general population appear early course of disease. Quality sleep quality life parallel these patients, such also represent a heavy burden for caregivers. Although alterations melatonin hypocretins (orexins) seem to play key role origin disturbances, etiology is multifactorial, including many factors as environment, behavior, treatments, comorbidities, among others. A comprehensive evaluation each patient essential design treatment that includes nonpharmacological pharmacological approaches. One particularly interesting point possibility pathogenesis AD, raising treating disorder may alter In this review, we present an update on bidirectional influence problems options. Behavioral measures, bright light therapy (BLT), melatonin, other drugs likely well known correctly managed by physicians charge patients. spite multiple treatments used, evidence efficacy scarce randomized double-blind placebo-controlled studies needed. Future directions establishment BLT protocols development with new mechanisms action, especially hypocretin receptor antagonists, agonists, molecules modulate clock. Keywords: Alzheimer disease, disorders, rhythm

Language: Английский

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