I can't understand how a doctor could say that a MAO-I does not have any effect on focus?
How someone who studied a lot of time could say that?
You have two MAO enzymes. MAO-B: It degrades (catabolism) and breaks dopamine mainly. The best drugs for inhibiting mao-b are selegiline and rasagiline. Dopamine produces pro-oxidant metabolites like DOPAC and DOPAL. MAO-B inhibition prevents dopamine catabolism and by doing so you protect your dopaminergic neurons from damage, since there is no MAO-B produced pro-oxidant dopamine metabolites. However selegiline the standard MAO-B inhibitors enhances dopamine in other ways different compared to rasagiline, selegiline increases BDNF and GDNF that are neuroprotectant by its own. Second seligine is a CAE a Catecholamine Enhancer. So you could try with selegiline, best way of taking it is orally 1 mg a day
MAO-A: This enzyme is so interesting because there is an interesting theory of the Warrior vs Worrier related to how the levels of this enzyme are, so you could be a low MAO-A person or a high levels MAO-A person, I still don't know well how the genetic polymorphism related to the level to this enzyme interacts with personality but you could search by your own on times when focus is working well on you.
MAO-A degrades Serotonin but it also degrades NOREPINEPHRINE. That's why MAO-A inhibitors not only could enhance mood in a serotonin related way (however as I understand of all the neurotransmitters serotonin is the absolute boss in terms of complexity, it is a f**cking neurotransmiter difficult to dominate).
Norepinephrine: as you could now Atomoxetine is a Norepinephrine reuptake inhibitor. This NT is of great importance in terms of focus and concentration, in the prefrontal cortex DOPAMINE is recycled by the Norepinephrine transporter (NET) and breaked by the COMT and MAO-A enzymes. The Dopamine transporter recycles dopamine in the mesolimbic area but its job in the prefrontal cortex is of an small if any importance, that's why you need some norepinephrine for focus and concentration and that's why Atomoxetine works for Slow cognitive tempo and ADD/ADHD, because it's enhances dopamine and norepinephrine in the needed areas for focus, concentration, working memory and organisational skills, the lovely prefrontal cortex.
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So you could enhance focus by: inhibition norepinephrine catabolism in the prefrontal cortex by the inhibition of MAO-A. COMT inhibition prevents norepinephrine and dopamine catabolism in the PFC also but there is only one pharmaceutical drug used in parkinsons disease that do such work Tolcapone (or Entacapone?) however the drug has some nasty sides like liver toxicity.
Atomoxetine does not prevent norepinephrine nor dopamine catabolism it only prevents the neurotransmitter from being recycled, so it accumulates in the synaptic cleft for more time.
The norepinephrine side effects: I know by personal experience, enhancing norepinephrine in some people could be a bad choice because it enhances irritability, impulsivity, anger, lack of patience with people, anxiety, sweating and vasoconstriction. I'm one of those guys, I had not tested my genes yet, but apparently of what I lack is from dopamine not norepinephrine.
However I have found a drug (or two) that enables me to handle norepinephrine very well, so I no longer suffer from side effects like irritability, anxiety or vasoconstriction
Guanfacine. You could start with low doses, I only use 0.025 mg x 2 a day.
If you want to take Atomoxetine or a MOA-A inhibitor mix it with low doses guanfacine, the drug will feel like a different animal
Guanfacine enhances the focus effect from stimulants and at the same time reduces side effects like anxiety, increased blood pressure and vasoconstriction
Another pharmaceutical option: Try to search for the "Ootosan Stack" several people uses it in a Facebook group. It consists of Moclobemide (A MAO-A inhibitor lacking of the typical tyramine side effects of old drugs of such class), Selegiline (MAO-B inhibitor, CAE enhancer, increases antioxidant enzymes and growth factors like GDNF and BDNF), Memantine (It is used for preventing tolerance and for regulating NMDA activation by excess Ca2++).
The other drug that I use everyday with Guanfacine is Memantine. 5 mg everyday, only side effect: increased blackouts from alcohol, so for now I'm using 2,5 mg without problems. It basically erases all the "mental noise" in your inner self, it is so easy to just sit down and put your mind in a silence mode. It combines so well with low doses guanfacine for me, so for now I don't feel any anxiety like in the past and my mind feels better, less "shit" going around thinking about self-distracting things like "why I am so imperfect?" "why I need to suffer from this, that was so bad...why it happened, the world is so bad", zero mental shit about useless things and in the long way it ables to "reset" your mind. You only will get rid of bad patterns of thoughts by having "victories", by learning by successes and preventing the thoughts associated to failure to coming back and dominate you, by doing so your brain will make less powerful the connections of such thoughts and will make more powerful and long-lasting the connections of the right ones.
My other lovely drug is Bromantane, however it has some problems 1) Tolerance develops with time 2) High price. But you are a different person in such drug, I think it even changed my personality to a more confident, organised and goal oriented person in the long-term. Bromantane works by increasing the enzyme Tyrosine Hydroxylase, this enzyme converts Tyrosine to L-DOPA. So your brain has more dopamine going around. However as an ADHD sufferer I can tell you, more dopamine in brain don't do nothing for my main problem: HOW TO DO BORING TASKS, HOW TO HAVE THE MOTIVATION FOR DOING BORING WORK THAT I DON'T CARE FOR LONG HOURS. That's why because for such thing you need to enhance dopamine concentration in the synaptic cleft to activate D2 receptors and other receptors. More dopamine in your monoamine vesicles or just in the mesolimbic area is not enough, you need dopamine in the synaptic cleft in the mesolimbic area and norepinephrine and dopamine in the PFC, again in the synaptic cleft for doing its job. That's why DRIs like methylphenidate and amphetamines (Dexedrine is the best of all amphetamines) are so good for taking care of ADD/ADHD symptoms.
I have tried Methylphenidate extended release and in my experience is so difficult to not get in love with the drug, I was able to control my muscles, respiration, extended focus and the most important I was not feeling like a robot all the time (this happened with Modafinil that I don't take anymore), I was able to change from tasks, so one minute I was a focus robot goal oriented machine and the next minute I was a social butterfly. However I felt the sides from Methylphenidate, it only started to work well when I combined it with guanfacine and Trimethylglycine (Betaine). I think have methylation issue.
So try to find the combination of drugs that works for you, you have your genes tested for you only need the money and the help of a good doctor.
Some of my mood issues similar to yours were erased with Bromantane+Memantine+Guanfacine.
I have also heard of similar problems get relieved by the concomitant use of Moclobemide+Memantine+Guanfacine. You looks like atomoxetine is overcharging your brain and peripheral nervous system from norepinephrine, apparently this is related to the MAO-A and COMT genes. Too much dopamine and norepinephrine in the PFC could lead to anxiety and concentration issues, thats was what happened to me with Methylphenidate, I was unable to understand what I was reading, my brain was only able to be in a zen mode, zero, blank state.
Edited by BieraK, 15 August 2019 - 07:47 AM.