The 3-iodothyronamine (T1AM) and 3-iodothryoacetic acid (TA1), are endogenous occurring compounds structurally related with thyroid hormones (THs, the pro-hormone T4 and the active hormone T3) initially proposed as possible mediators of the rapid effects of T3. However, after years from their identification, the physio-pathological meaning of T1AM and TA1 tissue levels remains an unsolved issue while pharmacological evidence indicates both compounds promote in rodents central and peripheral effects with mechanisms which remain mostly elusive. Pharmacodynamics of T1AM includes the recognition of G-coupled receptors, ion channels but also biotransformation into an active metabolite, i.e. the TA1. Furthermore, long term T1AM treatment associates with post-translational modifications of cell proteins. Such array of signaling may represent an added value, rather than a limit, equipping T1AM to play different functions depending on local expression of targets and enzymes involved in its biotransformation. Up to date, no information regarding TA1 mechanistic is available. We here review some of the main findings describing effects of T1AM (and TA1) which suggest these compounds interplay with the histaminergic system. These data reveal T1AM and TA1 are part of a network of signals involved in neuronal plasticity including neuroprotection and suggest T1AM and TA1 as lead compounds for a novel class of atypical psychoactive drugs.
Keywords: 3-Iodothyroacetic acid; 3-Iodothyronamine; Histamine; Neuroprotection; Thyroid hormone-related compounds; Thyroid hormones.
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