Tasimelteon: A selective and unique receptor binding profile

Abstract

Hetlioz(®) (tasimelteon) is the first approved treatment in the United States for Non-24-Hour Sleep-Wake Disorder (Non-24). We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes. Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively). Tasimelteon was also shown to have no appreciable affinity for more than 160 other pharmacologically relevant receptors and several enzymes.

Pharmacotherapy of Insomnia in Children

“…It has an affinity for human melatonin receptors MT1 and MT2, with a higher affinity for the latter. The clinical trials were done in blind adults with a circadian rhythm sleep disorder [22,23]. Safety and efficacy have not been established in pediatric patients.…”

Safety profile of tasimelteon, a melatonin MT1and MT2receptor agonist: pooled safety analyses from six clinical studies

“…Safety profile of tasimelteon, a melatonin MT 1 and MT 2 receptor agonist: pooled safety analyses from six clinical studies 1…”

“…Tasimelteon specifically binds with high affinity to the MT 1 and MT 2 melatonin receptors (with 2 --4 times greater affinity for the MT 2 receptor), which are thought to be involved in the control of circadian rhythms [1].…”

“…Tasimelteon also demonstrated the ability to phase advance circadian rhythms in a lab based study in healthy volunteers following an abrupt 5 h advance in sleep schedule, enabling subjects to fall asleep faster [1,5].…”

Orphan drug approvals of 2014: Europe and the United States

“…In contrast to ramelteon (Rozerem), which is approved for the treatment of insomnia, tasimelteon has only been approved for the orphan indication of non-24 h sleep--wake disorder in blind individuals [52,53]. Tasimelteon was originally being developed by Bristol-Myers Squibb for the treatment of insomnia but was licensed to Vanda Pharmaceuticals in 2004 [54].…”