I suspect a glutamate issue primarily, but that's because glutamate excess headaches are vasodilatory in nature. The glutamate excitoxicity threshold has many variables; GABA, dopamine, serotonin, aspartic acid, cellular energy, electrolytes, histamine, others.
Noopept is different from the racetams in its mechanism on glutamate. Now, if you look around, you'll see noopept frequently being mentioned as causing less or even preventing headaches, most of this information isn't entirely accurate because 'headache' is too vague, and what is typically being spoken of are acetylcholine related headaches, not glutamate.
I believe glutamate and/or histamine is the culprit behind noopept's known side effect of irritability.
In both cases of headache and irritability, co-occuring low GABA may be a factor. Perhaps low serotonin via temporary dips in serotonin or serotonin sensitivity as noopept is 'wearing off', perhaps only occuring in certain regions of the brain. The same could be said of dopamine, which is a gatekeeper of sorts of glutamate.
Noopept is often believed to be protective against glutamate excitotoxicity. There is a lot of conflicting information and studies. Given the amount of anecodotes I've read, I'm calling bullshit on noopept's glutamatergic neuroprotective properties - I'm not saying it's not at all true, but this is not something that is universally applicable because as I said, the excitotoxicity threshold is highly variable, so noopept is likelier to cause migrainelike or true migraine headaches in predisposed individuals and situations. 10mg noopept may leave you with a punishing headache one day, and nothing but awesome another day.
Nitrous oxide may have been another factor in the headaches occuring around physical and sexual activity. For whatever reason, noopept temporarily made you more vulnerable to a vasodilatory headache. Noopept has no obvious direct effect on vasodilation or constriction, but that isn't terribly useful information since there are many different ways it can have indirect influence.
Everything I've said is highly speculative. Right now this whole topic is speculative. As a migraineur and having a keen interest in learning about neurotransmitters in relation to headaches, I bring a slightly different perspective on nootropics to the table. I really wish we could have designated threads to noots, types of headaches and their various causes where we could all share what little tidbits of info we have and debate the problems. If I'm wrong about something I would like to know since I would personally benefit from that correction.
All I can say about other noots, if you've had this kind of experience with anything then avoid sunifiram until more study has been done on it. It may be fruitful to experiment on yourself with aniracetam and see if you get similar results as with noopept, since their activities with serotonin and dopamine are purported to be similar.
Edited by Duchykins, 14 July 2014 - 04:14 PM.