Procholinergic and memory enhancing properties of the selective norepinephrine uptake inhibitor atomoxetine.
...atomoxetine (0.3-3 mg/kg, i.p.),--increases in vivo extracellular levels of ACh in cortical but not subcortical brain regions. The marked increase of cortical ACh induced by atomoxetine was dependent upon norepinephrine alpha-1 and/or dopamine D1 receptor activation. We observed similar increases in cortical and hippocampal ACh release with methylphenidate (1 and 3 mg/kg, i.p.)--currently the most commonly prescribed medication for the treatment of ADHD--and with the norepinephrine uptake inhibitor reboxetine (3-30 mg/kg, i.p.). Since drugs that increase cholinergic neurotransmission are used in the treatment of cognitive dysfunction and dementias, we also investigated the effects of atomoxetine on memory tasks. We showed that, consistent with its cortical procholinergic and catecholamine-enhancing profile, atomoxetine (1-3 mg/kg, p.o.) significantly ameliorated performance in the object recognition test and the radial arm-maze test.
I am a big believer that Sluggish Cognitive Temp (SCT) aka Concentration Deficit Disorder (CCD) aka "The Daydreaming Disorder" is characterized by a lack of cortical alpha1 adrenergic agonism in the pre-frontal cortex. It's a little backwards of me to say this, but atomoxetine is the only known drug to show improvement in SCT/CCD. It's my theory to say that this is because those who daydream for no reason (and who just get jealous of everyone else's mental capacity to do important stuff in the right order without breaking a sweat) have low alpha1 receptor activity in the PFC.
To put this theory to test, if you have SCT/CCD, you can take some oxymetazoline up the nose, which has a pretty good selection of alpha1 over alpha 2 receptors. If it enhances memory and attention span and reduces daydreaming, I may be right.
Works for me, but the rebound sucks. Gives me a stuffy nose for a solid three days, so I switch to pseudophedrine for those three days. I also just feel weird shooting up nasal spray when I'm not sick. I have it in my car, in my desk, and in my nightstand for when I need to concentrate but suck at life. Also interesting is that alpha1 receptor activity increases estrogen receptor density... or at least antagonism does the opposite (sorry, lost my source, have to post it later), so it's safe to say it works the other way around. It's another reason why'd I'd opt to go with a selective norepinephrine reuptake inhibitor vs. a straight alpha1 agonist. Also another reason why I use oxymetazoline sparingly.
I just thought it was interesting that norepinephrine and acetylcholine activity were pals through D1 and Alpha1. D1 has a U shaped curve for (spatial) memory performance. There are more than one study out there that prove that, so I'll just go on to say that a non-U-shaped curve on memory of increased NE activity in the PFC probably has to do with the Alpha1 receptor. Also consider the higher affinity that norepinephrine has for alpha1 vs. D1 and because of that, alpha1 receptor activitation is a lot more likely from atomoxetine (whose affinity for NET vs. DAT is like 100-200x higher).
So yeah, I get pretty pumped when I realize that I don't need to be taking a whole lot of cholinergic supplements once I've got the alpha1 activity down. Still some, obviously, since ACh is necessary in the subcortical regions like the hippocampus for making good mental maps and stuff.