Atypical Antipsychotics, 5-HT7, and Cognition. Experiences?

[AlphaMethylPhenyl]

Yo, its been a while. I've read up on the atypical psychotics a lot recently because I have a dear friend taking Risperdal so I want to make sure he's taken care of well; this reading got me generally interested in the stuff, but more in terms of cognition. I used to think that anti-psychotics were evil, caging drugs with the only function of reducing pleasure, but I've come to realize through personal experience as well as that of my friend that too much of an endogenous psychoactive chemical can be just as bad or worse than too little.

Anyways, while reading I discovered a likely constituent of my friend's problem of decreased cognitive abilities in the form of D2 antagonism--which it can't be completely ascertained whether this makes him less productive in the moment but more productive overall due to, for instance, a conservation of finite energy his brain expends each day--, but I also read about the 5-HT7 receptor; apparently it affects cognitive abilities to a certain extent too; the thing I couldn't find anywhere was whether 5-HT7 antagonism or agonism was beneficial for cognition; which is it, or can it not be generalized (does each action benefit some processes)? Finding out that 5-HT7 antagonsim negatively affects cognition would kind of make me want to urge him to get off the medication ASAP, since its supposed to be semi-irreversible; yet this drug is apparently doing well for him.

This person I know, after my goading, was quite interested in finding out why there's a (discovered after I asked him) subtle change in his cognitive abilities. He thinks of me as the nueropsychopharmacology expert; I would give him all I know (D and alpha antagonism, not anti-chollinergic--thank G), but its interesting to me too. Can an expert please elaborate? It also strikes me as strange how these drugs can dumb down (major tranquilizers) but normalize behavior so as to improve performance in some ways; for instance, though he's definitely not as fluid overall, its certainly easier for him to perform when he's tired or hung over now, or in other words he isn't "hit so hard" by what most people would call a slight discomfort; as in before, such a discomfort would totally collapse his communication skills so people around him would think he was high. Yes this really is my friend, not I, but I was on one a few years ago and it helped.

Does anyone who was put on anti-psychotics want to share in terms of cognition (particularly Risperdal), and in general what the drug did for you--please don't waste time responding in flame and/or if you didn
t give the drug enough time? More importantly, what qualified, legal (including prescription) substances might you suggest to alleviate this? Thanks. Sorry for stream-of-thought writing. Have faith.
And please answer about 5-HT7!

 

[sekio]

I think the loss of activity.apathy is due to dopamine blockade, risperidone in particular is a real heavy hitter on the dopamine receptors which are known to be involved in motivation.

 

[Epsilon Alpha]

Well one thing we need to consider before we delve deeper into this topic is that there are multiple splice variants of 5HT7 (A, B, and D are expressed in humans). So we need to be careful to determine which one we're talking about for each ligand used.
http://en.wikipedia.org/wiki/5-HT7_receptor#Variants

However, for anti-psychotics I'm more inclined to say the bulk of their cognition blunting effects are due to antagonism of alpha adrenoreceptors, various dopamine receptors, MAChR, and possibly H1 antagonism (though being tired is separate from other processes).

The abundance of serotonin (5-HT) in the central nervous system can explain its role in the regulation of various functions, such as sleep, feeding, sexuality, emotional status, and pain. In addition, 5-HT localized in “cognitive pathways” with hippocampus and frontal cortex as the main target structures, is involved in learning and memory processes. Recent studies led to the discovery of various types and subtypes of receptors, differentially associated to cognitive mechanisms. Abundant data available reveals that the administration of 5-HT2A/2C and 5-HT4 receptor agonists, or 5-HT1A, 5-HT3 and 5-HT1B antagonists improves memory and has a facilitatory effect on learning in situations involving a high cognitive demand. On the contrary 5-HT2A/2C and 5-HT4 receptors antagonists, or 5-HT1A, 5-HT3 and 5-HT1B receptors agonists have opposite effects. Although these results are contradictory, or even opposite, it is important to take into account the effect of global, and unspecific, stimulation of serotonergic receptors and the activation of other neurotransmission systems, together with the type of task used, the way it is administered and the ligand affinity.

http://www.ncbi.nlm.nih.gov/pubmed/18243350

But, in rats at least 5HT7 antagonists appear to be pro-cognitive.

 

[bupropion]

How much Risperdal does your friend take and how long has he taken it for? I found that after a few years the problem with reduced cognition went away somewhat. Recently I was taking 20mg Haldol, 4-8mg Risperdal, and 40mg Geodon but now I am just taking 100-200mg Seroquel.

Methylphenidate can be used to alleviate side effects of antipsychotics. I am taking 27mg Concerta now.

 

[AlphaMethylPhenyl]

Thanks for the info. Apparently he's taking .5mg right now, but his doctor might be upping the dose to 1mg, much to his dismay; its a small dose, but he tells me he's really sensitive to how drugs affect his thinking. He was on methylphenidate earlier in his treatment while on Depakote, but it made him into a fascist egotistical machine. Maybe Risperdal would negate this side-effect? Also, he appreciated the methylphenidate save for the aforementioned effect, it bringing him up and down really fast, and it making his thinking (though ridiculously fast) less creative in a way. Perhaps modafinil would be best? Nootropics? Adaptogens? Ginkgo? He already drinks a fair amount of caffeine.