Luzindole (Synonyms: N-0774)

In addition to intrinsic antioxidant activities, melatonin evokes its effects through the G protein-coupled receptors MT1A (MT1) and MT1B (MT2).[1] Luzindole is a melatonin receptor antagonist that preferentially targets MT1B over MT1A (Ki values are = 10-27 and 158-513 nM, respectively).[2],[3],[4] Luzindole is used both in vitro and in vivo to evaluate the roles of melatonin receptor signaling in diverse pathways, including circadian rhythms, animal behavior, and melanophore response.[5],[6],[2]

Reference:
[1]. Chan, K.H., and Wong, Y.H. A molecular and chemical perspective in defining melatonin receptor subtype selectivity. International Journal of Molecular Sciences 14(9), 18385-18406 (2013).
[2]. Teh, M.T., and Sugden, D. Comparison of the structure-activity relationships of melatonin receptor agonists and antagonists: Lengthening the N-acyl side-chain has differing effects on potency on Xenopus melanophores. Naunyn-Schmiedeberg's Archives of Pharmacology 358(5), 522-528 (1998).
[3]. Dubocovich, M.L. Luzindole (N-0774): A novel melatonin receptor antagonist. Journal of Pharmacology and Experimental Therapeutics 246(3), 902-910 (1988).
[4]. Dubocovich, M.L., Masana, M.I., Iacob, S., et al. Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Naunyn-Schmiedeberg's Arch. Pharmacol. 355(3), 365-375 (1997).
[5]. Dubocovich, M.L., Yun, K., Al-Ghoul, W.M., et al. Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. The FASEB Journal 12(12), 1211-1220 (1998).
[6]. Laredo, S.A., Orr, V.N., McMackin, M.Z., et al. The effects of exogenous melatonin and melatonin receptor blockade on aggression and estrogen-dependent gene expression in male California mice (Peromyscus californicus). Physiology & Behavior 128, 86-91 (2014).