Circadian Rhythm Dysregulation and Restoration: The Role of Melatonin

Vasey, Clayton; McBride, Jennifer D.; Penta, Kayla

doi:10.3390/nu13103480

Cited by 128 publications

(92 citation statements)

References 80 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nonetheless, in a clinical context, a beneficial influence of agomelatine on sleep patterns quality and circadian rhythms would be helpful in the relief of GAD and the improvement of quality of life. The influence of agomelatine upon sleep onset and rhythms is mainly melatonergic (MT receptor stimulation) in nature, 161 – 163 but a contribution of 5-HT 2C receptor blockade should not be neglected. 85 , 110 , 111 , 164 In fact, blockade of 5-HT 2C receptors likely contributes to the short-term improvement by antidepressants like trazodone and mirtazapine of sleep, although their sedative properties – due to histamine H 1 antagonism – become problematic in some patients.…”

Section: General Discussion: Open Questions and Perspectivesmentioning

confidence: 99%

Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action

Millan

2022

Therapeutic Advances in Psychopharmacology

View full text Add to dashboard Cite

Generalized anxiety disorder (GAD), the most frequently diagnosed form of anxiety, is usually treated by cognitive-behavioural approaches or medication; in particular, benzodiazepines (acutely) and serotonin or serotonin/noradrenaline reuptake inhibitors (long term). Efficacy, compliance, and acceptability are, however, far from ideal, reinforcing interest in alternative options. Agomelatine, clinically employed in the treatment of major depression, expresses anxiolytic properties in rodents and was effective in the treatment of GAD (including severely ill patients) in several double-blind, short-term (12 weeks) and relapse-prevention (6 months) studies. At active doses, the incidence of adverse effects was no higher than for placebo. Agomelatine possesses a unique binding profile, behaving as a melatonin (MT1/MT2) receptor agonist and 5-HT2C receptor antagonist, yet recognizing neither monoamine transporters nor GABAA receptors. Extensive evidence supports a role for 5-HT2C receptors in the induction of anxious states, and their blockade likely plays a primary role in mediating the anxiolytic actions of agomelatine, including populations in the amygdala and bed nucleus of stria terminalis, as well as the hippocampus. Recruitment of MT receptors in the suprachiasmatic nucleus, thalamic reticular nucleus, and hippocampus appears to fulfil a complimentary role. Downstream of 5-HT2C and MT receptors, modulation of stress-sensitive glutamatergic circuits and altered release of the anxiogenic neuropeptides, corticotrophin-releasing factor, and vasopressin, may be implicated in the actions of agomelatine. To summarize, agomelatine exerts its anxiolytic actions by mechanisms clearly distinct from those of other agents currently employed for the management of GAD. Plain Language Summary How agomelatine helps in the treatment of anxiety disorders Introduction: • Anxiety disorders have a significant negative impact on quality of life. • The most common type of anxiety disorder, called generalized anxiety disorder (GAD), is associated with nervousness and excessive worry. • These symptoms can lead to additional symptoms like tiredness, sleeplessness, irritability, and poor attention. • GAD is generally treated through either cognitive-behavioural therapy or medication. However, widely used drugs like benzodiazepines and serotonin reuptake inhibitors have adverse effects. • Agomelatine, a well-established antidepressant drug, has shown anxiety-lowering (‘anxiolytic’) properties in rats and has been shown to effectively treat GAD with minimal side effects. • However, exactly how it acts on the brain to manage GAD is not yet clear. • Thus, this review aims to shed light on agomelatine’s mechanism of action in treating GAD. Methods: • The authors reviewed studies on how agomelatine treats anxiety in animals. • They also looked at clinical studies on the effects of agomelatine in people with GAD. Results: • The study showed that agomelatine ‘blocks’ a receptor in nerve cells, which plays a role in causing anxiety, called the 5-HT2C receptor. • Blocking this receptor, especially in specific brain regions such as nerve cells of the amygdala, bed nucleus of stria terminalis, and hippocampus, produced the anxiety reduction seen during agomelatine treatment. • Agomelatine also activates the melatonin (MT) receptor, which is known to keep anxiety in check, promote sleep, and maintain the sleep cycle. • Agomelatine should thus tackle sleep disturbances commonly seen in patients with GAD. • Beyond 5-HT2C and MT receptors, signalling molecules in nerve cells that are known to be involved in anxiety disorders (called ‘neurotransmitters’ and ‘neuropeptides’) are also affected by agomelatine. Conclusion: • Agomelatine’s anxiolytic effects are caused by mechanisms that are distinct from those of other medications currently used to treat GAD. • This explains its therapeutic success and minimal adverse side effects.

show abstract

Section: General Discussion: Open Questions and Perspectivesmentioning

confidence: 99%

Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action

Millan

2022

Therapeutic Advances in Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…Mel has several important protective and regulatory functions. In addition to its role in regulating sleep, Mel also protects ovarian function, regulates immune function, and has anti-aging and anti-tumor ( 40 – 42 ). In the female reproductive system, Mel plays an important role in normal physiology and protects against ovarian pathologies ( 21 , 43 ).…”

Section: Discussionmentioning

confidence: 99%

Melatonin prevents cyclophosphamide-induced primordial follicle loss by inhibiting ovarian granulosa cell apoptosis and maintaining AMH expression

Feng

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

Cyclophosphaty -45mide (Cyc) chemotherapy in young female cancer patients is associated with an increased risk of premature ovarian insufficiency (POI). This study was designed to investigate the protective role of melatonin (Mel) as an adjuvant against Cyc-induced POI. Female mice received a single intraperitoneal (i.p.) dose of Cyc (75 mg/kg). Mel protection was achieved in mice after i.p. injection of melatonin (50 mg/kg) every 24 h for four consecutive days prior to chemotherapy initiation and for 14 additional days. Ovarian reserve testing, hormonal assays for follicle-stimulating hormone, luteinizing hormone, and anti-Müllerian hormone (AMH), assessment of the oxidative stress status, and measurement of the relative expression of genes in PTEN/AKT/FOXO3a and mitochondrial apoptosis pathways were performed. The results showed that treatment with 50 mg/kg Mel significantly prevented Cyc-induced over-activation of primordial follicles by maintaining the plasma level of AMH and subsequently preventing litter size reduction in mice treated with Cyc chemotherapy. Importantly, Mel treatment significantly prevented ovarian granulosa cell loss by inhibiting the mitochondrial apoptotic pathway. Identifying the protective actions of Mel against Cyc-induced primordial follicle loss has important implications for fertility maintenance in young cancer patients undergoing chemotherapy.

show abstract

“…There are many benefits associated with melatonin. Firstly, melatonin can serve as an entrainment signal for the circadian system [ 156 ]; melatonin has established sleep-promoting effects, which means that it may serve as a therapeutic agent for treating sleep and circadian rhythm disorders [ 152 , 155 , 157 , 158 ]. Secondly, there is evidence indicating that melatonin could improve glucose homeostasis and insulin resistance in rodent animals [ 155 ].…”

Section: Treatment For T2dm and Ad Targeting Circadian Rhythmsmentioning

confidence: 99%

A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer’s Disease

Peng

Fan

Xie

et al. 2022

IJMS

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer’s disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we review the relationship among circadian rhythm disruption, T2DM and AD, and suggest that the occurrence and progression of T2DM and AD may in part be associated with circadian disruption. Then, we summarize the promising therapeutic strategies targeting circadian dysfunction for T2DM and AD, including pharmacological treatment such as melatonin, orexin, and circadian molecules, as well as non-pharmacological treatments like light therapy, feeding behavior, and exercise.

show abstract

Circadian Rhythm Dysregulation and Restoration: The Role of Melatonin

Cited by 128 publications

References 80 publications

Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action

Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action

Melatonin prevents cyclophosphamide-induced primordial follicle loss by inhibiting ovarian granulosa cell apoptosis and maintaining AMH expression

A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer’s Disease

Contact Info

Product

Resources

About