Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives

Comai, Stefano; Lopez‐Canul, Martha; Gregorio, Danilo De; Posner, Ada; Ettaoussi, Mohamed; Guarnieri, Fabrizia C.; Gobbi, Gabriella

doi:10.1016/j.phrs.2019.04.015

Cited by 42 publications

(29 citation statements)

References 163 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The phase-dependent response of T b to exogenous MLT may depend not only on the changes in the density of MLT receptors across the light–dark cycle, but also on the relative distribution and function of MT 1 and MT 2 receptors that control unique physiological responses in the brain, for example in sleep [21,22,23], anxiety [18,24], pain [25,26,57], and depression [28,58,59], and in the periphery, for example at the cardiovascular level [60,61].…”

Section: Discussionmentioning

confidence: 99%

Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle

Lopez‐Canul

Min

Posa

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1/MT2 receptor antagonist, luzindole, but not by the α1/MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb. These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb.

show abstract

Section: Discussionmentioning

confidence: 99%

Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle

Lopez‐Canul

Min

Posa

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, the pathophysiological function of MT1 and MT2 receptors is considered in the genesis of disturbances in the circadian rhythm and sleep structure, in particular, the paradoxical phase (REM sleep) [46,47], during which sudden death occurs in children [48]. For example, the destruction of MT1 and MT2 receptors in various brain structures involved in sleep mechanisms led to a reduction in the duration of REM sleep and impairment of behavior [49].…”

Section: Plos Onementioning

confidence: 99%

Sudden infant death syndrome: Melatonin, serotonin, and CD34 factor as possible diagnostic markers and prophylactic targets

et al. 2021

View full text Add to dashboard Cite

Sudden infant death syndrome (SIDS) is one of the primary causes of death of infants in the first year of life. According to the WHO’s data, the global infant mortality rate is 0.64–2 per 1,000 live-born children. Molecular and cellular aspects of SIDS development have not been identified so far. The purpose of this paper is to verify and analyze the expression of melatonin 1 and 2 receptors, serotonin (as a melatonin precursor), and CD34 molecules (as hematopoietic and endothelial markers of cardiovascular damage) in the medulla, heart, and aorta in infants who died from SIDS. An immunohistochemical method was used to investigate samples of medulla, heart, and aorta tissues of infants 3 to 9 months of age who died from SIDS. The control group included children who died from accidents. It has been shown that the expression of melatonin receptors as well as serotonin and CD34 angiogenesis markers in tissues of the medulla, heart, and aorta of infants who died from SIDS is statistically lower as compared with their expression in the same tissues in children who died from accidents. The obtained data help to clarify in detail the role of melatonin and such signaling molecules as serotonin and CD34 in SIDS pathogenesis, which can open new prospects for devising novel methods for predictive diagnosis of development and targeted prophylaxis of SIDS.

show abstract

“…It is worth mentioning that serotonin is a precursor for melatonin, which is also implicated in pain reduction and mood elevation [51,52]. It is, therefore, possible that some of the effects of increasing brain serotonin are processed via enhanced melatonin synthesis and function.…”

Section: Serotonin (5-hydroxytryptamine; 5-ht)mentioning

confidence: 99%

Targeting Serotonin1A Receptors for Treating Chronic Pain and Depression

Haleem

2019

View full text Add to dashboard Cite

The association of chronic pain with depression is becoming increasingly recognized. Treating both the conditions together is essential for an effective treatment outcome. In this regard, it is important to identify a shared mechanism involved in the association of chronic pain with depression. Central serotonin (5-hydroxytryptamine; 5-HT) neurotransmission has long been known to participate in the processing of signals related to pain. It also plays a key role in the pathogenesis and treatment of depression. Although functional responses to serotonin are mediated via the activation of multiple receptor types and subtypes, the 5-HT1A subtype is involved in the processing of nociception as well as the pathogenesis and treatment of depression. This receptor is located presynaptically, as an autoreceptor, on the perikaryon and dendritic spines of serotonin-containing neurons. It is also expressed as a heteroreceptor on neurons receiving input from serotonergic neurons. This article targets the 5-HT1A receptors to show that indiscriminate activation of pre and postsynaptic 5-HT1A receptors is likely to produce no therapeutic benefits; biased activation of the 5-HT heteroreceptors may be a useful strategy for treating chronic pain and depression individually as well as in a comorbid condition.

show abstract

Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives

Cited by 42 publications

References 163 publications

Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle

Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle

Sudden infant death syndrome: Melatonin, serotonin, and CD34 factor as possible diagnostic markers and prophylactic targets

Targeting Serotonin1A Receptors for Treating Chronic Pain and Depression

Contact Info

Product

Resources

About