Posted by zeugma on October 27, 2006, at 5:00:16
In reply to Re: Ca2+, posted by SLS on October 26, 2006, at 23:35:04
I had been wondering how SSRI's work on OCD when it seemed (following Robbins and Cools) that the OCD cognitive phenotype was insufficient D2 striatal stimulation. Fluvoxamine, which is also a sigma-1 agonist (Ki=36 nM) apparently leads to to a 7-10% upregulation of raclopride binding in the D2 receptors of the striatum in OCD patients.
This is very simplistic of course. But it was found that while 6-OH-dopamine lesions had no effect on the behavioral effects of NRI's, they blocked the effects of SSRI's in animal models.
I will post on the location and function of sigma-1 receptors later. The truth is that they are myststerious- sigma-knockout mice exhibited no evident abnormalities, and apparently these receptors share no homology with any other known type of receptor. Sigma-1 ligands are also famous for narrow, bell-shaped dose curves, which has probably made it difficult for these ligands to have their functions clarified.
-z
poster:zeugma
thread:696596
URL: http://www.dr-bob.org/babble/20061020/msgs/698123.html