Comment · Fri, November 18, 2016 · Ceretropic & Nootropics Depot
Has anyone utilized DA agonists long term(>2 weeks)? What has been your experience with their effects on mood?
Original post in this thread
hootnoot · 12 points
It has been shown that DA agonists have an effect on hedonic difficulties and depression. See below.
https://www.ncbi.nlm.nih.gov/pubmed/6751339
https://www.ncbi.nlm.nih.gov/pubmed/6172006
https://www.ncbi.nlm.nih.gov/pubmed/9295183
https://www.ncbi.nlm.nih.gov/pubmed/17187269
https://www.ncbi.nlm.nih.gov/pubmed/15999953
https://www.ncbi.nlm.nih.gov/pubmed/16814808
https://www.ncbi.nlm.nih.gov/pubmed/7871089
https://www.ncbi.nlm.nih.gov/pubmed/16959244
Any experiences?
Logically, DA agonists that are agonists both pre-synaptically and post-synaptically active will be aversive and generally shitty to begin with, that's a given. Sedation, fatigue, nausea are expected with DNsh agonism as these are autoreceptors that inhibit neurotransmission upon agonism. However, agonising D2L, for example, has been shown to be nootropic, mood enhancing, motivational and so forth. In-fact, there is a direct correlation between D2L expression and an array of pro-cognitive, mood and social effects. The problem with most DA agonists is an an affinity for both pre and post synaptic receptors. I speculate that upon down-regulation of the pre autoreceptors, with usage of >1 week, these drugs…
What they were answering
garmondbozia · 1 points
okay, those are interesting yet complicated answers. So for hootnoot, I take about 10 mg PD for mematine. I do find it can help my mood but also can cause some anxiety and outfriht fatigue especially when trying to do things like cardio. I also sweat a fuck ton more when I take mematine while doing cardio. I wonder if this has to do with the effects on C-AMP and aATP conversion.
I wonder which of methylphenidate or dexadrine like amphetamines are more addictive because of these differening mechanisms. I am suspecting that the amphetamine types would be, because of their signalling at the C-amp level. ....from what I read, the cAMP pathway has a lot to do with an addictive state. What or how would methylphenidatediffer with respect to an addictive state?
u/MisterYouAreSoDumb · Ceretropic & Nootropics Depot
Anxiety and fatigue are common side effects with Memantine. It most likely has do with with multiple systems. The NMDA, NACh, D2, and 5-HT3 receptors are likely involved. The mechanisms behind sweating are not fully understood, but most of the nerves that lead to the sweat glands are cholinergic or adrenergic. ACh is the main neurotransmitter that sets off sweating. However, nitric oxide has been implicated in it as well. Memantine has been shown to increase nitric oxide synthase, which could be the source of the sweating. That's just speculation on my part, though.
Dopamine releasers like amphetamine are certainly more addictive than a basic re-uptake inhibitor like methylphenidate. cAMP is definitely involved in the development of dependence and withdrawal symptoms. Adenylate cyclase activity, cAMP, and the Ca(2+) channels are all closely linked together, and they all play a role in dependence and withdrawal. Memantine modulate calcium influx by antagonizing the NMDA receptors, and also modulates cAMP through adenylate cyclase, by way of the D2 receptors. Since methylphenidate does not lead to as high levels of extracellular dopamine, and dopamine binding is what leads to downstream changes in adenylate cyclase, it does not have quite as much addictive potential as amphetamine. However, it's obviously more complex than that.