Inflammation in brain inhibited by new class of drugs

[MSUK]

Inflammation in brain inhibited by new class of potential drugs




Scientists at Emory University School of Medicine have identified a new group of compounds that may protect brain cells from inflammation linked to seizures and neurodegenerative diseases.

The compounds block signals from EP2, one of the four receptors for prostaglandin E2, which is a hormone involved in processes such as fever, childbirth, digestion and blood pressure regulation. Chemicals that could selectively block EP2 were not previously available. In animals, the EP2 blockers could markedly reduce the injury to the brain induced after a prolonged seizure, the researchers showed.

The results were published online this week in the Proceedings of the National Academy of Sciences Early Edition....Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/3349

[harry1]

Inflammation in brain inhibited by new class of potential drugs




Scientists at Emory University School of Medicine have identified a new group of compounds that may protect brain cells from inflammation linked to seizures and neurodegenerative diseases.

The compounds block signals from EP2, one of the four receptors for prostaglandin E2, which is a hormone involved in processes such as fever, childbirth, digestion and blood pressure regulation. Chemicals that could selectively block EP2 were not previously available. In animals, the EP2 blockers could markedly reduce the injury to the brain induced after a prolonged seizure, the researchers showed.

The results were published online this week in the Proceedings of the National Academy of Sciences Early Edition....Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/3349

Squiffy, i didn't see the name of the compound that they used as did i miss it in your posted article?

I'd like to post this story over at an ALS forum that i visit daily.

[cheerleader]

Here you go, Harry--the full article does not name the compounds they have tested, so I did some more research for you.
Here's the actual journal publication:
http://www.pnas.org/content/early/2012/02/07/1120195109

Here's the abstract---this is all being done in mouse models right now, and is very far away from clinical applications-

With interest waning in the use of cyclooxygenase-2 (COX-2) inhibitors for inflammatory disease, prostaglandin receptors provide alternative targets for the treatment of COX-2–mediated pathological conditions in both the periphery and the central nervous system. Activation of prostaglandin E2 receptor (PGE2) subtype EP2 promotes inflammation and is just beginning to be explored as a therapeutic target. To better understand physiological and pathological functions of the prostaglandin EP2 receptor, we developed a suite of small molecules with a 3-aryl-acrylamide scaffold as selective EP2 antagonists. The 12 most potent compounds displayed competitive antagonism of the human EP2 receptor with KB 2–20 nM in Schild regression analysis and 268- to 4,730-fold selectivity over the prostaglandin EP4 receptor. A brain-permeant compound completely suppressed the up-regulation of COX-2 mRNA in rat cultured microglia by EP2 activation and significantly reduced neuronal injury in hippocampus when administered in mice beginning 1 h after termination of pilocarpine-induced status epilepticus. The salutary actions of this novel group of antagonists raise the possibility that selective block of EP2 signaling via small molecules can be an innovative therapeutic strategy for inflammation-related brain injury.

Here's a link to a more lay person friendly article:
http://www.sciencedaily.com/releases/20 ... 122031.htm

cheer

[harry1]

Here you go, Harry--the full article does not name the compounds they have tested, so I did some more research for you.
Here's the actual journal publication:
http://www.pnas.org/content/early/2012/02/07/1120195109

Here's the abstract---this is all being done in mouse models right now, and is very far away from clinical applications-

With interest waning in the use of cyclooxygenase-2 (COX-2) inhibitors for inflammatory disease, prostaglandin receptors provide alternative targets for the treatment of COX-2–mediated pathological conditions in both the periphery and the central nervous system. Activation of prostaglandin E2 receptor (PGE2) subtype EP2 promotes inflammation and is just beginning to be explored as a therapeutic target. To better understand physiological and pathological functions of the prostaglandin EP2 receptor, we developed a suite of small molecules with a 3-aryl-acrylamide scaffold as selective EP2 antagonists. The 12 most potent compounds displayed competitive antagonism of the human EP2 receptor with KB 2–20 nM in Schild regression analysis and 268- to 4,730-fold selectivity over the prostaglandin EP4 receptor. A brain-permeant compound completely suppressed the up-regulation of COX-2 mRNA in rat cultured microglia by EP2 activation and significantly reduced neuronal injury in hippocampus when administered in mice beginning 1 h after termination of pilocarpine-induced status epilepticus. The salutary actions of this novel group of antagonists raise the possibility that selective block of EP2 signaling via small molecules can be an innovative therapeutic strategy for inflammation-related brain injury.

Here's a link to a more lay person friendly article:
http://www.sciencedaily.com/releases/20 ... 122031.htm

cheer

Thank you very much Cheerleader and i really do appreciate you taking the time to research this some more as that's really nice of you to do and i'll post your pnas.org link over at the ALS forum.

harry