8 replies to this topic

[Cosma]

Hi everyone!
For the past few weeks i've been reading nonstop trying to figure this one out, but can't seem to resolve this "enigma".
I was diagnosed during the years with OCD (not sure i fit this one), CFS (not really tired just very achy), and suffer from constant 24\7 tension feeling in my stomach.
Anyway let me get to the main point here which is that when taking Dimenhydrinate (a muscarinic acetylcholine antagonist), it seem to alleviate this constant wired\anxiety felling and some of the stomach tension i've had for the past 10 years.

Now my two main issues with Dimenhydrinate are; one- after taking a very low dose (25MG twice or thrice a day) i've woken up in the middle of the night with some sort of seizure feeling (electricity feeling in the brain for a few seconds, repeating every time i start falling asleep), which led me to think it might triggerd ADNFLE (Autosomal dominant nocturnal frontal lobe epilepsy), and two - Dimenhydrinate antagonise all muscarinic acetylcholine receptors, and it's probably only a part of the med's mechanism which give's me the positive symptoms relief im getting from it.

Just to inform you, i have taken dozens of different meds through the years, including SSRI's (most of them), antipsychotics (risperidal, sulpiride), antiepileptics (lamictal, tegretol...) and almost every supplement you can probably think of, and non of them felt like it "touched" the core problem like Dimenhydrinate does. actually, what led me to try Dimenhydrinate for the first place was noticing how much worse i'm feeling after taking the pro cholinergics- lecithin and pramiracetam.

So what do you guys think? what part of the med's action is the one that makes me feel better?
My main "suspect" at the moment is the M3 receptor, as according to what i was reading, it is very widespread in the gut, and the brain.
I know it's a very complicated issue, but i will greatly appreciate any insight any of you might have.

Thank you.

Edited by Cosma, 04 January 2014 - 05:56 AM.

[lourdaud]

An anti-cholinergic will increase dopamine, maybe you're on the low side. What you say about pramiracetam and lecithin points in this direction. Have you tried bupropion? I've had reactions similar to what you describe and bupropion is one of few AD's that really works.

[Cosma]

Actually i have tried bupropion a few years back and i guess it didn't really helped as i stopped it after a month or so.
as for the low dopamine theory, i can say that pro dopaminergics makes me feel really agitated after some time; ritalin was OK for 2-3 days, then i felt like i can't sit for one second... the same miserable feeling i get when taking pro-cholinergics. nicotine makes me feel the same.
Maybe dopaminergics upregulate one of my already upregulated nicotinic receptor in some way?
For some reason i suspect my problem has something to do with my nicotinic receptors (possibly a7), and already orderd galantamine and Nefiracetam in addition to antimuscarinics (tolterodine, Oxybutynin) to see what kind of reaction i get to each of them.
I'll update my reactions to them, but it will take a while as i ordered those from india (Nefiracetam from the US) and it will take some time to get here.

Edited by Cosma, 08 January 2014 - 05:44 AM.

[lourdaud]

For some reason i suspect my problem has something to do with my nicotinic receptors (possibly a7), and already orderd galantamine and Nefiracetam in addition to antimuscarinics (tolterodine, Oxybutynin) to see what kind of reaction i get to each of them.

Personally galantime is great for focus but makes me depressed at the same time. Nefiractam was ok for focus but tolerance developed quickly. This is why I suggested bupropion, the antagonism on some other nAChRs is supposed to up-regulate nicotinic a7 receptors. And bupropion doesn't have any tolerance issues, IME.

[Cosma]

Well, low dose salvia, which is a very dysphoric agent that most people hate, makes me feel "human" for about an hour.
each person has his own unique chemistry i guess, so ill have to try galantamine and Nefiractam and see what it does for me.

[lourdaud]

Well, low dose salvia, which is a very dysphoric agent that most people hate, makes me feel "human" for about an hour.
each person has his own unique chemistry i guess, so ill have to try galantamine and Nefiractam and see what it does for me.

I doubt you'll have very positive reactions to any of them if you didn't respond well to nicotine. But "YMMV" etc

[NeuroNootropic]

For some reason i suspect my problem has something to do with my nicotinic receptors (possibly a7), and already orderd galantamine and Nefiracetam in addition to antimuscarinics (tolterodine, Oxybutynin) to see what kind of reaction i get to each of them.

Personally galantime is great for focus but makes me depressed at the same time. Nefiractam was ok for focus but tolerance developed quickly. This is why I suggested bupropion, the antagonism on some other nAChRs is supposed to up-regulate nicotinic a7 receptors. And bupropion doesn't have any tolerance issues, IME.

I had tolerance issues with bupropion. I am sensitive to it and was taking Wellbutrin 150 mg XL once a day. In the first two weeks I felt great, my mood was improved, I was able to actually laugh, anhedonia was a bit decreased, I had more energy, was waking up at 8 hours refreshed (normally sleep for 10-12 hours and wake up sleepy), improved concentration and a list of other benefits. But, I was having side effects, particularly a pounding heart. It felt like I was on fight-or-flight 24/7.

After those two weeks passed I felt depressed, in a melancholic manner (I never had melancholia prior to Wellbutrin), irritable, even more anhedonic than my baseline, more anxious than usual, was sleeping 10-12 hours again.

I stayed on it for 5 weeks before stopping because I was much worse on it than off it. Over the past 3 years I have tried it several times again, and once even tried 300 mg XL and had too many side effects to list. Interestingly, I never had memory issues when I was on it. It seems a lot of people complain of short term memory loss.

Why do you think this happened? Any way to prevent the tolerance?

[lourdaud]

For some reason i suspect my problem has something to do with my nicotinic receptors (possibly a7), and already orderd galantamine and Nefiracetam in addition to antimuscarinics (tolterodine, Oxybutynin) to see what kind of reaction i get to each of them.

Personally galantime is great for focus but makes me depressed at the same time. Nefiractam was ok for focus but tolerance developed quickly. This is why I suggested bupropion, the antagonism on some other nAChRs is supposed to up-regulate nicotinic a7 receptors. And bupropion doesn't have any tolerance issues, IME.

I had tolerance issues with bupropion. I am sensitive to it and was taking Wellbutrin 150 mg XL once a day. In the first two weeks I felt great, my mood was improved, I was able to actually laugh, anhedonia was a bit decreased, I had more energy, was waking up at 8 hours refreshed (normally sleep for 10-12 hours and wake up sleepy), improved concentration and a list of other benefits. But, I was having side effects, particularly a pounding heart. It felt like I was on fight-or-flight 24/7.

After those two weeks passed I felt depressed, in a melancholic manner (I never had melancholia prior to Wellbutrin), irritable, even more anhedonic than my baseline, more anxious than usual, was sleeping 10-12 hours again.

I stayed on it for 5 weeks before stopping because I was much worse on it than off it. Over the past 3 years I have tried it several times again, and once even tried 300 mg XL and had too many side effects to list. Interestingly, I never had memory issues when I was on it. It seems a lot of people complain of short term memory loss.

Why do you think this happened? Any way to prevent the tolerance?

I don't think this is because tolerance sets in. Two weeks is really the time it takes for bupropion to work so if you didn't like it then it's probably not for you. The fact that you felt great the first weeks might even suggest that you benefit from lower norepinephrine levels.

[NeuroNootropic]

For some reason i suspect my problem has something to do with my nicotinic receptors (possibly a7), and already orderd galantamine and Nefiracetam in addition to antimuscarinics (tolterodine, Oxybutynin) to see what kind of reaction i get to each of them.

Personally galantime is great for focus but makes me depressed at the same time. Nefiractam was ok for focus but tolerance developed quickly. This is why I suggested bupropion, the antagonism on some other nAChRs is supposed to up-regulate nicotinic a7 receptors. And bupropion doesn't have any tolerance issues, IME.

I had tolerance issues with bupropion. I am sensitive to it and was taking Wellbutrin 150 mg XL once a day. In the first two weeks I felt great, my mood was improved, I was able to actually laugh, anhedonia was a bit decreased, I had more energy, was waking up at 8 hours refreshed (normally sleep for 10-12 hours and wake up sleepy), improved concentration and a list of other benefits. But, I was having side effects, particularly a pounding heart. It felt like I was on fight-or-flight 24/7.

After those two weeks passed I felt depressed, in a melancholic manner (I never had melancholia prior to Wellbutrin), irritable, even more anhedonic than my baseline, more anxious than usual, was sleeping 10-12 hours again.

I stayed on it for 5 weeks before stopping because I was much worse on it than off it. Over the past 3 years I have tried it several times again, and once even tried 300 mg XL and had too many side effects to list. Interestingly, I never had memory issues when I was on it. It seems a lot of people complain of short term memory loss.

Why do you think this happened? Any way to prevent the tolerance?

I don't think this is because tolerance sets in. Two weeks is really the time it takes for bupropion to work so if you didn't like it then it's probably not for you. The fact that you felt great the first weeks might even suggest that you benefit from lower norepinephrine levels.

How do you know if it's from lower norepinephrine levels? I found this study done on rats that found that the norepinephrine firing rate in the locus coeruleus decreased after 2 days but recovered after 14 days:

Bupropion' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pubmed/18708076']Bupropion is widely used in the treatment of depression. There are, however, limited data on its long-term effects on monoaminergic neurons and therefore the mechanism of its delayed onset of action is at present not well understood. The present study was conducted to examine the effects of prolonged bupropion administration on the firing activity of dorsal raphe nucleus (DRN), locus coeruleus (LC), and ventral tegmental area (VTA) neurons. Spontaneously firing neurons were recorded extracellularly in rats anesthetized with chloral hydrate. Bupropion (30 mg/kg/day) was administered using subcutaneously implanted minipumps. In the DRN, the firing rate of serotonin (5-HT) neurons was significantly increased after 2, 7 and 14 days of administration. The suppressant effect of LSD was significantly diminished after the two-day regimen, indicating a desensitization of 5-HT1A autoreceptors. In the LC, the firing rate of norepinephrine (NE) neurons was significantly attenuated after a 2-day regimen, but recovered progressively over 14 days of administration. The suppressant effect of clonidine on NE neuronal firing was significantly attenuated in rats treated with bupropion for 14 days, indicating a desensitization of alpha2-adrenoceptors. In the VTA, neither 2 nor 14 days of bupropion administration altered the firing and burst activity of dopamine neurons. These results indicate that bupropion, unlike 5-HT reuptake inhibitors, promptly increased 5-HT neuronal activity, due to early desensitization of the 5-HT1A autoreceptor. The gradual recovery of neuronal firing of NE neurons, due to the desensitization of alpha2-adrenoceptors, in the presence of the sustained increase in 5-HT neuronal firing, may explain in part the delayed onset of action of bupropion in major depression.

→ source (external link)

Based on this study and your speculation, what do you suggest I take to decrease norepinephrine in the LC?

Edited by NeuroNootropic, 10 January 2014 - 01:36 AM.