Thyronamines—Past, Present, and Future

After their initial discovery in the early 1950's, thyronamines (TAM), a class of endogenous signalling compounds exhibiting structural similarity to the thyroid hormone L-thyroxine, are now back in the focus of basic and clinical research. Numerous prompt pharmacological effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria and reduction of fat mass as well as promising therapeutic potential in the experimental prophylaxis and treatment of stroke have already been demonstrated in rodent experimental models. This review article summarizes the currently still somewhat scattered data on TAM, trying to yield a complete and updated picture of the current state of TAM research, which addresses issues on TAM biosynthesis, receptors, signalling and therapeutically relevant targets such as energy metabolism and the cardiovascular system. Thyronamines (TAMs) are a newly identified class of endogenous signaling compounds. Their structure is identical to that of thyroid hormone and deiodinated thyroid hormone derivatives, except that TAMs do not possess a carboxylate group. Despite some initial publications dating back to the 1950s, TAMs did not develop into an independent area of research until 2004, when they were rediscovered as potential ligands to a class of G protein-coupled receptors called trace-amine associated receptors. Since this discovery, two representatives of TAMs, namely 3-iodothyronamine (3-T1AM) and thyronamine (T0AM), have been detected in vivo. Intraperitoneal or central injection of 3-T1AM or T0AM into mice, rats, or Djungarian hamsters caused various prompt effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria, and reduction of fat mass. Although their physiological function remains elusive, 3-T1AM and T0AM have already revealed promising therapeutic potential because they represent the only endogenous compounds inducing hypothermia as a prophylactic or acute treatment of stroke and might thus be expected to cause fewer side effects than synthetic compounds. This review article summarizes the still somewhat scattered data on TAMs obtained both recently and more than 20 yr ago to yield a complete and updated picture of the current state of TAM research.