Posted by AndrewB on December 4, 2000, at 10:00:41
In reply to alpha-1 and D2 related? , posted by JohnL on December 2, 2000, at 5:56:12
John,
Thank you for posting this interesting abstract. It is established that both serotnergic and andrenergic ADs upregulate postsynaptic D2 receptor activity. This increase in D2 (D3?) activity possibly is ultimately responsible for the mood elevating properties of these ADs.
One thing that is interesting in this study is that they achieved the D2 effect with alpha-1 agonism within a week but not with 5-HT uptake inhibitors. Serotonergic drugs take some time usually (2 weeks plus) to exhibit their mood benefit. Likewise these serotenergic drugs take some time to upregulate the D2 receptors. The reason for this seems to be that the serotonergic system does not act directly on the D2 receptors but rather via modulating the NMDA receptors which in turn modulate the D2 receptors.
This study suggest that there may be a rather direct connection between the alpha1 system and the D2 receptors.BTW, I've been very interested lately in the NMDA system's involvement in D2/D3 modulation. It seems that, in some cases at least, NMDA dyregulation is resposible for AD non-response or poop out. It seems likely that lithium's ability to modulate NMDA activity (via control of calcium influx) explains it effectiveness as an augmentation agent to ADs. This to me points to the potential usefullness other drugs that modulate NMDA activity. For example, memantine modulates NMDA activity via control of calcium influx like lithium but without any of lithium's nasty side effects (lithium is a dirty drug).
Again thanks for the posting,
AndrewB
poster:AndrewB
thread:49799
URL: http://www.dr-bob.org/babble/20001130/msgs/49888.html