MT-2 (Melanotan 2 Acetate) - 10mg

Neuropathic pain (NP) represents a considerable clinical challenge, profoundly impacting patients' quality of life. Presently, pharmacotherapy serves as a primary approach for NP alleviation, yet its efficacy often remains suboptimal. Melatonin (MLT), a biologically active compound secreted by the pineal gland, has long been associated with promoting and maintaining sleep. Although recent studies suggest analgesic effects of MLT, the underlying mechanism remains largely unknown, particularly its impact on the cortex. In this study, we induced an NP model in mice through spared nerve injury (SNI) and observed a considerable, dose-dependent alleviation in NP symptoms following intraperitoneal or anterior cingulate cortex (ACC) administration of MLT. Our findings further indicated that the NP management of MLT is selectively mediated by MLT-related receptor 2 (MT 2 R), rather than MT 1 R, o

Why linked: The title contains the resolved identity “MT-2 -”.

Melatonin, a neurohormone secreted by the pineal gland and regulated by the suprachiasmatic nucleus (SCN) of the hypothalamus, is synthesized and directly released into the cerebrospinal fluid (CSF) of the third ventricle (3rdv), where it undergoes rapid absorption by surrounding tissues to exert its physiological function. The hippocampus, a vital structure in the limbic system adjacent to the ventricles, plays a pivotal role in emotional response and memory formation. Melatonin MT 1 and MT 2 receptors are G protein-coupled receptors (GPCRs) that primarily mediate melatonin's receptor-dependent effects. In comparison to the MT 1 receptor, the widely expressed MT 2 receptor is crucial for mediating melatonin's biological functions within the hippocampus. Specifically, MT 2 receptor is implicated in hippocampal synaptic plasticity and memory processes, as well as neurogenesis and axogenes

Why linked: The title contains the resolved identity “MT-2 -”.

The pathophysiological function of the G-protein coupled melatonin MT 1 and MT 2 receptors has not yet been well-clarified. Recent advancements using selective MT 1 / MT 2 receptor ligands and MT 1 /MT 2 receptor knockout mice have suggested that the activation of the MT 1 receptors are mainly implicated in the regulation of rapid eye movement (REM) sleep, whereas the MT 2 receptors selectively increase non-REM (NREM) sleep. Studies in mutant mice show that MT 1 knockout mice have an increase in NREM sleep and a decrease in REM sleep, while MT2 knockout mice a decrease in NREM sleep. The localization of MT 1 receptors is also distinct from MT2 receptors; for example, MT 2 receptors are located in the reticular thalamus (NREM area), while the MT 1 receptors in the Locus Coeruleus and lateral hypothalamus (REM areas). Altogether, these findings suggest that these two receptors not only hav

Why linked: The title contains the resolved identity “MT-2 -”.

G protein-coupled receptors (GPCRs) transmit extracellular signals into cells by activating G protein- and β-arrestin-dependent pathways. Extracellular signal-regulated kinases (ERKs) play a central role in integrating these different linear inputs coming from a variety of GPCRs to regulate cellular functions. Here, we investigated human melatonin MT 1 and MT 2 receptors signaling through the ERK1/2 cascade by employing different biochemical techniques together with pharmacological inhibitors and siRNA molecules. We show that ERK1/2 activation by both receptors is exclusively G protein-dependent, without any participation of β-arrestin1/2 in HEK293 cells. ERK1/2 activation by MT 1 is only mediated though G i/o proteins, while MT 2 is dependent on the cooperative activation of G i/o and G q/11 proteins. In the absence of G q/11 proteins, however, MT 2 -induced ERK1/2 activatio

Why linked: The title contains the resolved identity “MT-2 -”.

Previous studies have reported the effects of melatonin mainly in male rodents. However, the effect of sex on the effect of melatonin remains unknown. The purpose of this study was to evaluate the role of sex in the antiallodynic effect of melatonin under neuropathic pain conditions. Intrathecal melatonin reduced both evoked and spontaneous pain in female and male neuropathic mice, with a significantly greater effect in female mice. Selective blockade of spinal melatonin MT 2 , but not MT 1 , receptors abated the antiallodynic effect of melatonin in both sexes. In contrast, blockade of spinal opioid receptors abated the antiallodynic effect of melatonin in male mice and partially in female mice. Notably, ovariectomy eliminated the antiallodynic effect of melatonin in female mice. Additionally, 17β-estradiol or estrogen receptor-α agonist PPT treatment, but not estrogen recept

Why linked: The title contains the resolved identity “MT-2 -”.

Temporomandibular joint osteoarthritis (TMJOA) is one of the most common diseases causing chronic pain in the oral and maxillofacial region. So far, there are few ways to relieve the pain of TMJOA. Melatonin (MT) has a good analgesic effect in many diseases, including fibromyalgia, neuropathic pain, chronic headache, and burn pain, with very low acute toxicity and side effects. This study was to investigate the role and mechanism of MT in TMJOA chronic pain. In rats TMJOA chronic pain occurred at day 14 after an intra-temporomandibular joint injection of monosodium iodoacetate, which we previously reported. The enzyme-linked immunosorbent assay results showed that MT levels were higher in the synovial fluid from patients and rats with TMJOA as compared with those from control. Fluorescent retrograde tracing (Dil) identified that upregulation of MT type 2 receptor (MT 2 R) in trigeminal g

Why linked: The title contains the resolved identity “MT-2 -”.

In crystal structures of melatonin MT 1 and MT 2 receptors, a lipophilic subpocket has been characterized which accommodates the phenyl ring of the potent agonist 2-phenylmelatonin. This subpocket appears a key structural element to achieve high binding affinity and selectivity for the MT 2 receptor. A series of 2-arylindole ligands was synthesized to probe the requirements for the optimal occupation and interaction with the 2-phenyl binding pocket. Thermodynamic integration simulations applied to MT 1 and MT 2 receptors in complex with the α-naphthyl derivative provided a rationale for the MT 2 -selectivity and investigation on the binding mode of a couple of atropisomers allowed to define the available space and arrangement of substituents inside the subpocket. Interestingly, more hydrophilic 2-aza-substituted compounds displayed high binding affinity and molecular dynamics simul

Why linked: The title contains the resolved identity “MT-2 -”.

Nocturnal asthma is characterized by heightened bronchial reactivity at night, and plasma melatonin concentrations are higher in patients with nocturnal asthma symptoms. Numerous physiological effects of melatonin are mediated via its specific G protein-coupled receptors (GPCRs) named the MT 1 receptor, which couples to both G q and G i proteins, and the MT 2 receptor, which couples to G i . We investigated whether melatonin receptors are expressed on airway smooth muscle; whether they regulate intracellular cyclic AMP (cAMP) and calcium concentrations ([Ca 2+ ] i ), which modulate airway smooth muscle tone; and whether they promote airway smooth muscle cell proliferation. We detected the mRNA and protein expression of the melatonin MT 2 but not the MT 1 receptor in native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by RT-PCR, immunoblot

Why linked: The title contains the resolved identity “MT-2 -”.

Understanding ligand selectivity and efficacy at melatonin (MT 1 , MT 2 ) and serotonin (5-HT 2C ) receptors remains a key challenge in central nervous system (CNS) drug discovery. Ligands combining MT 1 /MT 2 agonism with 5-HT 2C antagonism are of therapeutic relevance in depression and circadian rhythm disorders. This review provides a comprehensive overview of ligands reported for these receptors in ChEMBL, with an emphasis on compounds evaluated across multiple targets. A pharmacophore-based approach was applied to group ligands by shared features, revealing pharmacomodulations influencing receptor selectivity and polypharmacology. Together, these insights can inspire the rational design of selective or polypharmacological ligands, offering new opportunities for multitarget drug discovery.

Why linked: The title contains the resolved identity “MT-2 -”.

Circadian rhythms disturbance is widely observable in patients with major depression (MD) and is also associated with depression vulnerability. Of them, disturbed melatonin secretion rhythm is particularly relevant to MD and is strongly phase-locked to core body temperature (CBT) rhythm. Here we aim to study the specific role of each melatonin receptor (MT 1 and MT 2 ) subtype in melatonin regulation of circadian CBT and its possible relationship with depressive-like behaviors. MT 1 -/- , MT 2 -/- and WT (C57BL/6) mice were used.  Anhedonia, using the sucrose intake test, circadian CBT, environmental place preference (EPP) conditioning and vulnerability to chronic social defeat stress (CSDS) procedure were studied. Moreover, the antidepressant effects of reboxetine (15 mg/kg/day, i.p.) for three weeks or ketamine (15 mg/kg i.p. every four days, 4 doses in total) were studi

Why linked: The title contains the resolved identity “MT-2 -”.

Melatonin is produced during the night and regulates sleep and circadian rhythms. Loss-of-function variants in MTNR1B , which encodes the melatonin receptor MT 2 , a G protein-coupled receptor (GPCR), are associated with an increased risk of type 2 diabetes (T2D). To identify specific T2D-associated signaling pathway(s), we profiled the signaling output of 40 MT 2 variants by monitoring spontaneous (ligand-independent) and melatonin-induced activation of multiple signaling effectors. Genetic association analysis showed that defects in the melatonin-induced activation of Gα i1 and Gα z proteins and in spontaneous β-arrestin2 recruitment to MT 2 were the most statistically significantly associated with an increased T2D risk. Computational variant impact prediction by in silico evolutionary lineage analysis strongly correlated with the measured phenotypic effect of each va

Why linked: The title contains the resolved identity “MT-2 -”.

CD4 + forkhead box P3 (FOXP3) + regulatory T cells (Tregs) are essential in maintaining immune tolerance and suppressing excessive immune responses. Tregs also contribute to tissue repair processes distinct from their roles in immune suppression. For these reasons, Tregs are candidates for targeted therapies for inflammatory and autoimmune diseases, and in diseases where tissue damage occurs. MT-2 cells, an immortalized Treg-like cell line, offer a model to study Treg biology and their therapeutic potential. In the present study, we use clustered regularly interspaced palindromic repeats (CRISPR)-mediated knockdown of FOXP3 in MT-2 cells to understand the transcriptional and functional changes that occur when FOXP3 is lost and to compare MT-2 cells with primary human Tregs. We demonstrate that loss of FOXP3 affects the transcriptome of MT-2 cells and that FOXP3's potential downstream tar

Why linked: The title contains the resolved identity “MT-2 -”.