Replies to post #183051 on Anavex Life Sciences Corp (AVXL)

[XenaLives]

Don't have a "scientific background" per se, but it's using the serotonin receptor. A quick google gives this:

Role of 5-HT2A receptor antagonists in the treatment of insomnia.
Vanover KE1, Davis RE.
Author information
Abstract
Insomnia encompasses a difficulty in falling asleep (sleep-onset insomnia) and/or a difficulty in staying asleep (SMI). Several selective serotonin-2A (5-HT2A) receptor antagonists have been in development as potential treatments for SMI. However, none have shown a sufficiently robust benefit-to-risk ratio, and none have reached market approval. We review the role of the 5-HT2A mechanism in sleep, the preclinical and clinical data supporting a role for 5-HT2A receptor antagonism in improving sleep maintenance, and the status of 5-HT2A receptor antagonists in clinical development. Overall, the polysomnography data strongly support an increase in slow-wave sleep and a decrease in waking after sleep onset following treatment with 5-HT2A receptor antagonists, although it has been more difficult to show subjective improvements in sleep with these agents. The incidence and prevalence of SMI, whether primary or secondary to psychiatric, neurologic, or other medical conditions, will increase as our population ages. There will be an increased need for safe and efficacious treatments of insomnia characterized by difficulty maintaining sleep, and there remains much promise for 5-HT2A receptor antagonism to play a role in these future treatments.

KEYWORDS:
5-HT2A; insomnia; serotonin; slow-wave sleep; wake after sleep onset

https://www.ncbi.nlm.nih.gov/pubmed/23616706

Abstract
Serotonin (5-hydroxytryptamine; 5-HT) plays key roles in sleep–wakefulness regulation. Evidence indicates that 5-HT2 receptors are involved mainly in non-rapid eye movement sleep (NREMS) regulation and respiratory control. Here, we investigated the relative contribution of 5-HT2A, 5-HT2B, and 5-HT2C receptor subtypes to NREMS and breathing during sleep, using 5-HT2 subtype-selective ligands in wild-type (5-HT2A+/+) and knock-out (5-HT2A–/–) mice that do not express 5-HT2A receptors. Acute blockade of 5-HT2A receptors induced an increase in NREMS in 5-HT2A+/+ mice, but not 5-HT2A–/– mutants, which spontaneously expressed less NREMS than wild-type animals. In 5-HT2A+/+ mice, 5-HT2B receptor blockade produced a reduction of NREMS, whereas receptor activation induced an increase in this sleep stage. These effects were less pronounced in 5-HT2A–/– mice, indicating a lower sensitivity of 5-HT2B receptors in mutants, with no change in 5-HT2B mRNA. Blockade of 5-HT2C receptors had no effect on NREMS in both strains. In addition, an increase in EEG power density after sleep deprivation was observed in 5-HT2A+/+ mice but not in 5-HT2A–/– mice. Whole-body plethysmographic recordings indicated that 5-HT2A receptor blockade in 5-HT2A+/+ mice reduced NREMS apneas and bradypneas that occurred after sighs. In contrast, in 5-HT2A–/– mutants, NREMS apneas were not modified, and bradypnea after sighs were more pronounced. Our results demonstrate that 5-HT exerts a 5-HT2B-mediated facilitation of NREMS, and an influence respectively inhibitory on NREMS and facilitatory on sleep apnea generation, via 5-HT2A receptors. Moreover, 5-HT2A gene knock-out leads to functional compensations yielding adaptive changes opposite to those caused by pharmacological blockade of 5-HT2A receptors in 5-HT2A+/+ mice.

www.jneurosci.org/content/25/49/11231.long

So it's an approach that's been around for a while. Messing with Serotonin hasn't been anything but a temporary solution in the history of pharma and can result in mitochondrial dysfunction with LT use.

I'll stick with cellular homeostasis and Anavex.