Melatonin receptor and fatty acid amide hydrolase (MT-FAAH)

The Melatonin receptor and fatty acid amide hydrolase (MT-FAAH) system is a dual therapeutic target approach that combines the activation of melatonin receptors (MT1 and MT2) with the inhibition of the enzyme fatty acid amide hydrolase (FAAH) [1, 3]. Melatonin receptors are G protein-coupled receptors (GPCRs) primarily involved in the regulation of circadian rhythms and the provision of neuroprotective and antioxidant effects [4]. FAAH is the principal serine hydrolase enzyme responsible for the metabolic breakdown of the endocannabinoid anandamide; its inhibition elevates endocannabinoid tone, which helps modulate pain, anxiety, and neuroinflammation [3, 5]. \n\nHybrid ligands designed for this dual target, such as UCM1341, aim to achieve synergistic therapeutic effects in treating multifactorial conditions like Alzheimer's disease, neuropathic pain, and glaucoma [2, 3]. By simultaneously enhancing melatonin signaling and preventing the degradation of endocannabinoids, these agents promote the resolution of inflammation and protect neuronal tissues more effectively than single-target treatments [1, 4]. In preclinical models of glaucoma, dual MT-FAAH modulators have demonstrated sustained reduction of intraocular pressure, highlighting their potential for ocular therapy [2]. This multitarget strategy represents a modern pharmacological effort to address complex disease pathologies by stabilizing both the circadian and endocannabinoid regulatory systems [5].

Other names

Melatonin-FAAH dual targetMT-FAAH hybrid targetMT1/MT2/FAAHMelatonin receptor-fatty acid amide hydrolaseMelatonin-FAAH multitarget ligands

Multi-target ligand activity involving agonism of the MT1 and MT2 melatonin receptors and simultaneous inhibition of the fatty acid amide hydrolase (FAAH) enzyme, leading to elevated levels of endogenous melatonin signaling and fatty acid amides like anandamide.