September 02, 2008 - Somaxon Pharmaceuticals, Inc. (Nasdaq:SOMX), a specialty pharmaceutical company focused on the in-licensing and development of proprietary product candidates for the treatment of diseases and disorders in the fields of psychiatry and neurology, announced that data from a pharmacological profiling study relating to doxepin, the active ingredient in the company’s product candidate Silenor for the treatment of insomnia, were presented yesterday at the 21st European College of Neuropsychopharmacology (ECNP) Congress. The data presented at the ECNP Congress are from a study that examined the in vitro pharmacological profile of doxepin. The study evaluated the relative affinity and functional activity of doxepin at various central nervous system (CNS) targets known to play a role in its overall pharmacological profile.
The results demonstrate that doxepin has high affinity for and potent antagonistic activity at the human H1 histamine receptor, which is thought to be a primary mediator of the sleep-wake cycle. In addition, doxepin was shown to have lower or little affinity for a number of other CNS binding sites.
It is hypothesized that at the point in the circadian cycle during which the release of histamine and wakefulness are both naturally reduced, blocking the H1 receptor can further reduce wakefulness and promote the initiation and maintenance of sleep. The high potency of doxepin as an H1 antagonist represents the likely mechanism for its sleep-promoting effects and provides a potential explanation for its efficacy in humans at oral doses of 1 mg, 3 mg and 6 mg, the doses evaluated in the company’s clinical trials of Silenor for the treatment of insomnia. In addition, the relative selectivity of doxepin for H1 as compared to a number of other neuropharmacological sites may account for the low incidence in such clinical trials of adverse events that have been associated with higher doses (25 mg to 50 mg) of doxepin... [PDF] Somaxon's Press Release -
