MT1 Agonist

Ramelteon is a potent, highly selective, and orally active agonist of MT1/MT2 with Ki values of 14 and 112 pM, respectively. Ramelteon has the potential for the research of insomnia. Ramelteon consistently reduces sleep onset after long-term treatment, with no next-morning residual effects or rebound insomnia or withdrawal symptoms upon discontinuation.

2-Iodomelatonin is a potent agonist of melatonin receptor 1 (MT1) with a K_i value of 28 pM, it is more 5-fold selective for MT₁ over MT₂. 2-iodomelatonin can be used to identify, characterize and localize melatonin binding sites in the brain and peripheral tissues.

ACH-000143 is a potent and orally active melatonin receptor agonist, with EC₅₀ values of 0.06 nM and 0.32 nM for MT1 and MT2, respectively.

Piromelatine (Neu-P11) is a melatonin MT₁/MT₂ receptor agonist, serotonin 5-HT_1A/5-HT_1D agonist, and serotonin 5-HT_2B antagonist. Piromelatine (Neu-P11) possesses sleep promoting, analgesic, anti-neurodegenerative, anxiolytic and antidepressant potentials. Piromelatine (Neu-P11) also possesses pain-related P2X3, TRPV1, and Nav1.7 channel-inhibition capacities.

UCM 608 is a high affinity melatonin (MT) membrane receptor agonist. The pKi values for MT1 and MT2 are 10.7 and 10.4.

Agomelatine-d₆ is deuterium labeled Agomelatine. Agomelatine is a specific agonist of MT1 and MT2 receptors .

Ramelteon-d₅ is deuterium labeled Ramelteon. Ramelteon is a potent, highly selective, and orally active agonist of MT1/MT2 with K_i values of 14 and 112 pM, respectively. Ramelteon has the potential for the research of insomnia. Ramelteon consistently reduces sleep onset after long-term treatment, with no next-morning residual effects or rebound insomnia or withdrawal symptoms upon discontinuation.

Agomelatine-d₃ is the deuterium labeled Agomelatine. Agomelatine (S-20098) is a specific agonist of MT1 and MT2 receptors with K_is of 0.1, 0.06, 0.12, and 0.27 nM for CHO-hMT1, HEK-hMT1, CHO-hMT2, and HEK-hMT2, respectively. Agomelatine is a selective 5-HT2C receptor antagonist with pKis of 6.4 and 6.2 at native (porcine) and cloned, human 5-HT2C receptors, respectively.

Agomelatine-d₄ is the deuterium labeled Agomelatine. Agomelatine (S-20098) is a specific agonist of MT1 and MT2 receptors with K_is of 0.1, 0.06, 0.12, and 0.27 nM for CHO-hMT1, HEK-hMT1, CHO-hMT2, and HEK-hMT2, respectively. Agomelatine is a selective 5-HT2C receptor antagonist with pKis of 6.4 and 6.2 at native (porcine) and cloned, human 5-HT2C receptors, respectively.

Melatonin receptor agonist 1 (compound 20c) is a potent melatonin receptor (MT) agonist, with K_i values of 108 nM (MT₂) and 1140 nM (MT₁).

7-Desmethyl-3-hydroxyagomelatine (3-Hydroxy-7-desmethyl agomelatine), a metabolite of Agomelatine, has less activity than Agomelatine. Agomelatine is a melatonergic (MT1 and MT2) agonist and serotonergic (5HT2C) antagonist.

UCM 793 is a non-selective MT1/MT2 receptor agonist (pK_is: 9.09 (MT1 receptor); 9.19 (MT2 receptor)). UCM793 increases the number of episodes and decreases the length of the episodes of wakefulness. UCM 793 influences quality of the vigilance states. UCM 793 decreases sleep onset without having an effect on NREM sleep maintenance.

TIK-301 (PD-6735) is a chlorinated melatonin derivative and a potent, high-affinity and orally active melatonin MT₁ and MT₂ receptors agonist with K_is of 0.081 nM and 0.042 nM, respectively. TIK-301 is also a 5-HT_2B/5-HT_2C receptors antagonist with antidepressant action. TIK-301 has the potential for sleep disorders and other circadian rhythm disorders treatment.

6-Chloromelatonin is a potent melatonin receptor agonist with greater metabolic stability than melatonin. 6-Chloromelatonin compete for [³H]-melatonin and 2-[¹²⁵I]-iodomelatonin binding to MT1 receptors (pK_i=8.9 and 9.1, respectively). 6-Chloromelatonin compete for [³H]-melatonin binding to MT2 receptors (pK_i=9.77).