A piperazine to become an anti-depressant?

[toe]

This one is in listed in the pipeline at phrma.org as being in trials to become a new anti-depressant. Here's the pubmed on what it does- I know you guys can dumb this back down into something a humanities specialist can comprehend.

Synthesis and SAR of adatanserin: novel adamantyl aryl- and heteroarylpiperazines with dual serotonin 5-HT(1A) and 5-HT(2) activity as potential anxiolytic and antidepressant agents.

Abou-Gharbia, MA, Childers, WE,
Fletcher, H, McGaughey, G, Patel, U, Webb, MB, Yardley, J, Andree, T, Boast, C, Kucharik, RJ, Marquis, K, Morris H, Scerni R, Moyer, JA.

Chemical Sciences and CNS Disorders, Wyeth-Ayerst Research, CN 8000, Princeton, New Jersey 08543-8000, USA. Abougam@war.wyeth.com

Several novel functionalized adamantyl aryl- and heteroarylpiperazine derivatives were prepared and examined in various receptor binding and behavioral tests to determine their serotonin receptor activities. Many compounds demonstrated modest to high affinity for 5-HT(1A) receptors, with compounds 9, 13, 23, 33, 34, and 43 being the most potent at this site. Compound 1, 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl adamantyl-1-carboxylate, demonstrated relatively high affinity for 5-HT(1A) receptors (K(i) = 8 nM) and acceptable selectivity versus D(2) receptors (K(i) = 708 mM); however, it lacked in vivo activity in serotonergic behavioral models. In contrast, compounds 9 (WY-50,324, SEB-324, adatanserin), adamantyl-1-carboxylic acid 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamide, and 13, adamantyl-1-carboxylic acid 2-[4-(2-methoxyphenyl)-1-piperazinyl]ethylamide, demonstrated high affinity for 5-HT(1A) binding sites (K(i) = 1 nM for both) and moderate affinity for 5-HT(2) receptors (K(i) = 73 and 75 nM, respectively). Both compounds also demonstrated partial 5-HT(1A) agonist activity in vivo in rat serotonin syndrome and 5-HT(2) antagonist activity in quipazine- and DOI-induced head shake paradigms. The selective 5-HT(1A) partial agonist and 5-HT(2) antagonist activity of 9 was accompanied by significant anxiolytic activity in an animal conflict model. On the basis of this profile, compound 9 entered development as a combined anxiolytic and antidepressant agent.

By name alone, it makes me think of mianserin, but I don't know how that works either. Although I've snuck into the theater to see a few scenes on just about every non-MAOI anti-depressant ever to play on the American screen, I've really only sat through the credits and returned for encores on a few of the highly selective neurotransmitter reuptake inhibitors.


At the very least, please tell me I pegged it correctly as a piperazine this time?

[zapatista]

there is already as piperazine being used as an anti depressant. trazadone has been on the market for quiet some time.
Z

[toe]

I wasn't aware of that, thanks.

That doesn't bode very well for this one, unfortunately. Trazadone is a shitty anti-depressant- you rarely hear of it being prescribed for more than sleep-onset insomnia.