Parnate, no desire to talk

[Jimminy_Billy_Bob]

Ok so I've read a few posts where people have described that parnate makes them untalkative in social situations, I must say that is exactly what I am experiencing, and it was the same when i took nardil. Its true, the parnate makes you not care about others for some reason, I feel more secure in myself but less caring or interested in others. So my question is is there anything I can add to the parnate which will help this? Caffiene does help a bit, so does nicotine (not really a good option due to bad health effects).

At the moment I take magnesium and zinc for general health and deficiency, but I have a wide range of nootropics just sitting around waiting to be used. Anything that hits dopamine would be of some use i guess..

[Freesix88]

This happened with me on cymbalta. I'm already very quiet guy most of the time I don't know what to say to people. When I increased my dosage from 30mg to 60mg
I experienced more energy (probably due norepinephrine) but less interests in things..
-also sexual side effects as usual.
-my dilated pupils omg. they were huge and they stayed huge.
-constipation
-dry mouth and eyes (annoying when I use contacts)
-careless (less anxiety but not in a good way)
uh the positive effects? nothing.

I don't know what you can mix with parnate..

[Vini Vidi Vici]

crap.....i had a good post, and i deleted it. i was gonna say that yeah your description totally fits my experience on Parnate.

Sadly, there is not much stuff one could add to Parnate, due to its Tyramine crisis thingy. Nicotine and Caffeine both help me considerably, im hoping to aquire some 4mg nicotine gum in the future so i don't have to smoke like every 3 hours to feel better....oh and Nicotine, by itself, itsn't barely dangerous to your health. Its the smoke and carcinogens in Tobacco that are bad for your health. Pure nicotine won't do anything bad, except raise your blood pressure slightly...just like any other stimulant.

Theres TONS of stuff i WOULD add (to enhance dopamine)....but i can't because of the potential for a hypertensive crisis. Im not sure if Green Tea has ever caused problems, but some catechins such as EGCG are capable of inhibiting COMT (one of the enzymes that degrades dopamine). So u might get more dopamine from that.... a 5ht2c and 5ht6/5ht7 antagonist would help alot with enhancing dopaminergic function...as serotonin activates these receptors resulting in decreased dopaminergic function.

I really hope u can figure something out....cuz im pretty sure im gonna switch to something different. Parnate is simply not as effective as i had hoped..... I'd almost rather just take a low-dose SSRI + Dexedrine, Adderral, or Ritalin. It would do nearly the same thing....and honestly, from my experience, the combination felt MORE dopaminergic than Parnate ever has. Id just gotta use an NMDA antagonist and maybe MAO-
B inhibitor to enhance effects/decrease tolerance to the Adderral/Dexedrine.

what is the point of an MAOI if it doesnt do anything? its just like a slightly dopaminergic SSRI, for me at least. I know for some people it works great, and i hope it continues to do so.

[db0255]

VVV, you should try Prozac.

I don't notice any social effects (positive/negative) on Parnate, just the alleviation of depression. Only med to work for that except for Prozac. I'm just happy that I'm not irritable, can get out of bed, do more stuff, and not wanna eat and sleep all day. It's great!

[Vini Vidi Vici]

Originally Posted by db0255

VVV, you should try Prozac.

I don't notice any social effects (positive/negative) on Parnate, just the alleviation of depression. Only med to work for that except for Prozac. I'm just happy that I'm not irritable, can get out of bed, do more stuff, and not wanna eat and sleep all day. It's great!

you know...its funny, ive never tried it. ive always wondered about it....because its been shown to act differently to all the other SSRIs, like you have mentioned previously. But what really interests me is its supposed 5ht2c antagonism....that is the difference. This might cause it to be more activating, as opposed to other SSRIs. I would really like to try, at least just to see if its different, at least a low dose....---

db0255-- have u taken any other SSRIs? how did Prozac differ/compare to them in terms of activation, side effects, and overall effectiveness?

[db0255]

OK, Prozac is the weirdest drug I've ever taken, and if you've followed my posts, it explains a lot. Definitely the best, but still weird.

I say weird, because no one can explain pharmacologically why Prozac worked the way it did for me. I've taken Remeron, which is the 5-ht2c antagonism that you want, and it didn't compare. It got rid of the flinch/startle anxiety, but left me feeling weird/drugged.

Anyway, Prozac was activating as ****, and when I say that I mean it. It was more activating than a stimulant for me, but keep in mind I've only "done" caffeine and parnate. My brain was flipped ON with Prozac.

Other SSRIs I've tried were Lexapro, Paxil, Zoloft, and even Celexa. I've tried Strattera, St. John's Wort and Cymbalta also. A lot of crap. I had a lot of side effects with most, weight gain being the worst, and somnolescence being second. I'd say none of them were really activating at all.
Also, in terms of effectiveness, Prozac was transformative and the definition of a miracle drug for those of you on here. Honestly, it's the standard, and what others that have gotten probably the same relief (and advantages socially) with other drugs have seen in a best possible scenario. I wouldn't want you to get your hopes up like it will do the same for you, but I highly suggest reading Listening to Prozac to be pleasantly informed.
Also, just for the fact that a small percentage of people have such a good result like I do, I'm surprised it isn't the first SSRI tried. You've tried so many drugs, that it's like...why the **** not, no? None have worked, this might be the best for you!

[Vini Vidi Vici]

Originally Posted by db0255

OK, Prozac is the weirdest drug I've ever taken, and if you've followed my posts, it explains a lot. Definitely the best, but still weird.

I say weird, because no one can explain pharmacologically why Prozac worked the way it did for me. I've taken Remeron, which is the 5-ht2c antagonism that you want, and it didn't compare. It got rid of the flinch/startle anxiety, but left me feeling weird/drugged.

Anyway, Prozac was activating as ****, and when I say that I mean it. It was more activating than a stimulant for me, but keep in mind I've only "done" caffeine and parnate. My brain was flipped ON with Prozac.

Other SSRIs I've tried were Lexapro, Paxil, Zoloft, and even Celexa. I've tried Strattera, St. John's Wort and Cymbalta also. A lot of crap. I had a lot of side effects with most, weight gain being the worst, and somnolescence being second. I'd say none of them were really activating at all.
Also, in terms of effectiveness, Prozac was transformative and the definition of a miracle drug for those of you on here. Honestly, it's the standard, and what others that have gotten probably the same relief (and advantages socially) with other drugs have seen in a best possible scenario. I wouldn't want you to get your hopes up like it will do the same for you, but I highly suggest reading Listening to Prozac to be pleasantly informed.
Also, just for the fact that a small percentage of people have such a good result like I do, I'm surprised it isn't the first SSRI tried. You've tried so many drugs, that it's like...why the **** not, no? None have worked, this might be the best for you!

dude i know!!! ive tried pretty much everything there is, except prozac so theres no point in not trying it really (at a low dose in combination with a Dopaminergic Stimulant). the only reason i used to not want to take it was because of the 5ht2c antagonism....i assumed that due to its antagonism, the increased serotonin would not be able to downregulate 5ht2c receptors, and thus i would be stuck with overactive 5ht2c activity forever. but now after researching it more, i see that 5ht2c doesnt downregulate/upregulate in the same manner as most other receptors....and ive already been on Parnate for a month now....so if i take Prozac, im probably not gonna have the initial side effects that people get at the start of treatment, due to my already present Serotonin recepetor downregulation....

the only thing im worried about:: - at my next doctors appointment, im hoping to discuss a medication change. i have many different ideas/combinations that i believe may help,......i was gonna go for Dexedrine+Tramadol+Memantine. a long shot, i know....but there is a much higher chance i would get Dexedrine+Prozac.

[jim_morrison]

Originally Posted by db0255

OK, Prozac is the weirdest drug I've ever taken, and if you've followed my posts, it explains a lot. Definitely the best, but still weird.

I say weird, because no one can explain pharmacologically why Prozac worked the way it did for me. I've taken Remeron, which is the 5-ht2c antagonism that you want, and it didn't compare. It got rid of the flinch/startle anxiety, but left me feeling weird/drugged.

Anyway, Prozac was activating as ****, and when I say that I mean it. It was more activating than a stimulant for me, but keep in mind I've only "done" caffeine and parnate. My brain was flipped ON with Prozac.

Other SSRIs I've tried were Lexapro, Paxil, Zoloft, and even Celexa. I've tried Strattera, St. John's Wort and Cymbalta also. A lot of crap. I had a lot of side effects with most, weight gain being the worst, and somnolescence being second. I'd say none of them were really activating at all.
Also, in terms of effectiveness, Prozac was transformative and the definition of a miracle drug for those of you on here. Honestly, it's the standard, and what others that have gotten probably the same relief (and advantages socially) with other drugs have seen in a best possible scenario. I wouldn't want you to get your hopes up like it will do the same for you, but I highly suggest reading Listening to Prozac to be pleasantly informed.
Also, just for the fact that a small percentage of people have such a good result like I do, I'm surprised it isn't the first SSRI tried. You've tried so many drugs, that it's like...why the **** not, no? None have worked, this might be the best for you!

How were the sexual side effects on prozac? were they less than the other SSRI's you tried?

[rocknroll714]

Originally Posted by Jimminy_Billy_Bob

Ok so I've read a few posts where people have described that parnate makes them untalkative in social situations, I must say that is exactly what I am experiencing, and it was the same when i took nardil. Its true, the parnate makes you not care about others for some reason, I feel more secure in myself but less caring or interested in others. So my question is is there anything I can add to the parnate which will help this? Caffiene does help a bit, so does nicotine (not really a good option due to bad health effects).

At the moment I take magnesium and zinc for general health and deficiency, but I have a wide range of nootropics just sitting around waiting to be used. Anything that hits dopamine would be of some use i guess..

See this (if you haven't already):

Originally Posted by rocknroll714

You just described my experience with Nardil to a tee.

And this (from here -- good read):

Originally Posted by rocknroll714

To my surprise, I experienced powerful apathy even on the prominently dopaminergic MAOI antidepressant phenelzine (Nardil). I had no motivation, drive, desire.. etc, I couldn't even listen to music. There was just no emotion there. This was approximately two months in and it had indeed fully kicked in with maximum therapuetic benefits. It was both great as it entirely abolished my anxiety, but horrific at the same time as the emotion and pleasure of life were inhibited nearly as effectively. On top of that even though my SA was just annihilated, I didn't have the pro-social desire to make it even matter (it was more like anti-social..). I just stopped caring about everything. I promptly quit the wretched and "pointless" (as I like to call it - what's the point in being alive if you can't FEEL alive?) drug and swore I'd never let another serotonergic like such entire my body ever again.

These serotonergic antidepressants are saturating dopamine activity in the pleasure centers somehow, resulting in these effects.. apathy/anhedonia/emotional blunting/whatever, which, for us social phobics who need drive, reinforcement, and pleasure to sufficiently desire and enjoy social encounters, is not good at all. The primary mechanisms I see for this are prolactin secretion via serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptor activation (prolactin inhibits dopamine in the brain), inhibition of dopamine and norepinephrine release through activation of excitatory 5-HT2C receptors located on inhibitory GABAergic interneurons, and perhaps some involvement of 5-HT6 and 5-HT7 receptors which produce depressive/anxiogenic effects and in a few studies have been shown to interact with dopamine, though the implications of this have not been well-defined.

Like you said, any dopaminergic (and possibly noradrenergic as well to some extent) should be useful in combating the effect. I think a more direct approach is necessary though.. that of which I have in mind being selective 5-HT2C blockade. And I say selective because most available 5-HT2C antagonists are also 5-HT2A antagonists (e.g., mirtazapine, mianserin, trazodone, nefazodone, atypical antipsychotics, cyproheptadine, etc), and 5-HT2A receptors are very good at enhancing dopamine release in the pleasure centers, hence, you don't exactly want to block them. Although 5-HT2A antagonists are paradoxically antidepressant through disinhibition of norepinephrine release in the locus cereulus which subsequently enhances 5-HT1A activity in the dorsal raphe nucleus, I personally don't believe antagonizing 5-HT2A is worth the trade off in neurotransmission -- after all, antidepressant and anhedonic responses are mediated via completely separate pathways, and the SSRIs being my prime example, a drug can produce both effects simultaneously. Indeed, I found mirtazapine, a combined 5-HT2A and 5-HT2C antagonist, despite being a decent antidepressant, to produce an effect I described as "dose-dependently draining all my dopamine away". Yuck. I didn't find it to be particularly useful at all in reversing Nardil-induced apathy either, despite high expectations at the time.

Anyway, there are only a few available 5-HT2C antagonists I know of that don't also block 5-HT2A receptors, and they include agomelatine, tramadol, and dimebolin. Fluoxetine is also a 5-HT2C antagonist without actions on 5-HT2A receptors in addition to its SSRI effects, but I have concerns regarding its potency for this action. I'm not sure that it's strong enough to be sufficiently useful, and it can't be used to counteract 5-HT2C activation of other serotonergic antidepressants like in your case tranylcypromine obviously. I'd say agomelatine is currently the most practical -- and very promising at that -- solution. I'm probably never taking any generalized pro-serotonergic antidepressant ever again, but if I were to do so, it would be in combination with agomelatine.

[crayzyMed]

Great post rocknroll. Yeah i agree that agomelatine is our best option as an 5HT2C antagonist. Multiple doses a day would be needed tough with its short half life.

I never really jumped on the "anti 5HT2A bandwagon".

[rocknroll714]

Originally Posted by Vini Vidi Vici

crap.....i had a good post, and i deleted it. i was gonna say that yeah your description totally fits my experience on Parnate.

Sadly, there is not much stuff one could add to Parnate, due to its Tyramine crisis thingy. Nicotine and Caffeine both help me considerably, im hoping to aquire some 4mg nicotine gum in the future so i don't have to smoke like every 3 hours to feel better....oh and Nicotine, by itself, itsn't barely dangerous to your health. Its the smoke and carcinogens in Tobacco that are bad for your health. Pure nicotine won't do anything bad, except raise your blood pressure slightly...just like any other stimulant.

Theres TONS of stuff i WOULD add (to enhance dopamine)....but i can't because of the potential for a hypertensive crisis. Im not sure if Green Tea has ever caused problems, but some catechins such as EGCG are capable of inhibiting COMT (one of the enzymes that degrades dopamine). So u might get more dopamine from that.... a 5ht2c and 5ht6/5ht7 antagonist would help alot with enhancing dopaminergic function...as serotonin activates these receptors resulting in decreased dopaminergic function.

I really hope u can figure something out....cuz im pretty sure im gonna switch to something different. Parnate is simply not as effective as i had hoped..... I'd almost rather just take a low-dose SSRI + Dexedrine, Adderral, or Ritalin. It would do nearly the same thing....and honestly, from my experience, the combination felt MORE dopaminergic than Parnate ever has. Id just gotta use an NMDA antagonist and maybe MAO-
B inhibitor to enhance effects/decrease tolerance to the Adderral/Dexedrine.

what is the point of an MAOI if it doesnt do anything? its just like a slightly dopaminergic SSRI, for me at least. I know for some people it works great, and i hope it continues to do so.

SSRI/SNRI + NDRI/NDRA >>> MAOI both in terms of efficacy and tolerability, as well as in safety regarding food and drug interactions. Also throw in a benzodiazepine or pregabalin/gabapentin if you'd like to replicate phenelzine's GABAergic actions and you'll have quite a killer antidepressant/anxiolytic combination. Add in agomelatine as well and damn.. you'll have me drooling.

Originally Posted by Vini Vidi Vici

...i assumed that due to its antagonism, the increased serotonin would not be able to downregulate 5ht2c receptors, and thus i would be stuck with overactive 5ht2c activity forever...

A receptor will generally never desensitize to or past the difference in the intensity it's being stimulated and its normal level of activity. In other words, 5-HT2C will not downregulate back to normal or lower in response to any duration of SSRI treatment -- you have to block it with an antagonist.

Originally Posted by Vini Vidi Vici

...but now after researching it more, i see that 5ht2c doesnt downregulate/upregulate in the same manner as most other receptors...

5-HT2A and 5-HT2C are different from other GPCRs in that they desensitize in response both to agonists and antagonists, but I think you knew that already. I wonder how in the hell they ever manage to upregulate.. I guess that's mediated through absence of binding of any kind of ligand. Only explanation I can think of at least.

[crayzyMed]

Originally Posted by rocknroll714

SSRI/SNRI + NDRI/NDRA >>> MAOI both in terms of efficacy and tolerability, as well as in safety regarding food and drug interactions. Also throw in a benzodiazepine or pregabalin/gabapentin if you'd like to replicate phenelzine's GABAergic actions and you'll have quite a killer antidepressant/anxiolytic combination. Add in agomelatine as well and damn.. you'll have me drooling.

Id say an NDRA+Benzo+Agomelatine would be great enough, no need for the SSRI. The SSRI's we were all going to flush in the toilet.

[crayzyMed]

Originally Posted by rocknroll714

SSRI/SNRI + NDRI/NDRA >>> MAOI both in terms of efficacy and tolerability, as well as in safety regarding food and drug interactions. Also throw in a benzodiazepine or pregabalin/gabapentin if you'd like to replicate phenelzine's GABAergic actions and you'll have quite a killer antidepressant/anxiolytic combination. Add in agomelatine as well and damn.. you'll have me drooling.



A receptor will generally never desensitize to or past the difference in the intensity it's being stimulated and its normal level of activity. In other words, 5-HT2C will not downregulate back to normal or lower in response to any duration of SSRI treatment -- you have to block it with an antagonist.



5-HT2A and 5-HT2C are different from other GPCRs in that they desensitize in response both to agonists and antagonists, but I think you knew that already I wonder how in the hell they manage to upregulate.. I guess that's mediated through absence of binding of any kind of ligand. Only explanation I can think of at least.

Hypericum can be used to upregulate 5HT2A and 5HT1A. Stress hormones are also capable of upregulating 5HT2A.

[rocknroll714]

Originally Posted by crayzyMed

Id say an NDRA+Benzo+Agomelatine would be great enough, no need for the SSRI:D. The SSRI's we were all going to flush in the toilet:p.

Okay, replace the SSRI with either tandospirone or an opioid (or both :D).

• NDRI/NDRA + Tandospirone + Agomelatine + Opioid + Benzodiazepine

I'd personally also throw in an MAO-B inhibitor for long-term dopaminergic neuroprotection (as well as for blockade of NDRA neurotoxicity if say amphetamine as an example is used) and an NMDA antagonist for tolerance (not to mention further therapeutic benefits -- ketamine for treatment-resistant depression comes to mind), plus supplements like your antioxidants, B-vitamins, amino acids, and so forth.

I love daydreaming about crazy awesome regimens, as you all can tell :P

[crayzyMed]

Originally Posted by rocknroll714

Okay, replace the SSRI with either tandospirone or an opioid (or both ).

I love daydreaming about crazy regimens, as you all can tell :P

Your not the only one. And yeah those sound like a great alternative.

[Jimminy_Billy_Bob]

Just out of curiosity, have any of you guys tried cutting gluten and dairy out of your diet for a period of at least a month? There is increasing evidence that the proteins in these foods worsen and are even the main cause of depression, anxiety, autistic and schizophrenic symptomology. This is due to a number of reasons, one being that these foods break down into exorphins that mess around normal brain activity and prevent natural endorphins from working. Also the proteins damage and inflame the gut lining causing malabsorption problems, so the body cant assimilate key nutrients, particularly those needed for proper mental function.

I have been avoiding gluten and casein containing foods for about a week now and the transformation I am seeing is nothing short of miraculous, that combined with the effects of the parnate kicking in ofcourse.

The diet is tough though as most foods contain gluten and casein, but it is definately worth a shot. IT may be hard to start off with too as if you are allergic to these foods then you crave them almost like a drug as they make you feel better in the short term. If you cut them out cold turkey you can go through withdrawal which can bring on a wide variety of nasty symptoms, in my case I found that I was constantly thinking about the foods and how much I wanted to eat them, and the fact that I had to avoid them made me angry and depressed. Once you get past those first couple of days its smooth sailing though.

[jim_morrison]

I'm no fan of SSRI's, but I have to admit that in retrospect lexapro (oddly enough) helped to lessen my agoraphobia but not social-situation anxiety. I found myself able to leave the house more often on it. Mirtazapine is the complete opposite for me, it doesn't help with my OCD/agoraphobia at all, and I actually find myself more apathetic towards life, and less willing to leave the house. If mirtazapine didn't help me sleep, then honestly I'd throw it in the trash in a heartbeat.

[jim_morrison]

Originally Posted by rocknroll714

SSRI/SNRI + NDRI/NDRA >>> MAOI both in terms of efficacy and tolerability, as well as in safety regarding food and drug interactions. Also throw in a benzodiazepine or pregabalin/gabapentin if you'd like to replicate phenelzine's GABAergic actions and you'll have quite a killer antidepressant/anxiolytic combination. Add in agomelatine as well and damn.. you'll have me drooling.

I agree with this, it's not that SSRI's are inherently bad, there just too incomplete.

As for a GABAergic my personal preferance would be for clonazepam due to the long half life.

[crayzyMed]

Originally Posted by Jimminy_Billy_Bob

Just out of curiosity, have any of you guys tried cutting gluten and dairy out of your diet for a period of at least a month? There is increasing evidence that the proteins in these foods worsen and are even the main cause of depression, anxiety, autistic and schizophrenic symptomology. This is due to a number of reasons, one being that these foods break down into exorphins that mess around normal brain activity and prevent natural endorphins from working. Also the proteins damage and inflame the gut lining causing malabsorption problems, so the body cant assimilate key nutrients, particularly those needed for proper mental function.

I have been avoiding gluten and casein containing foods for about a week now and the transformation I am seeing is nothing short of miraculous, that combined with the effects of the parnate kicking in ofcourse.

The diet is tough though as most foods contain gluten and casein, but it is definately worth a shot. IT may be hard to start off with too as if you are allergic to these foods then you crave them almost like a drug as they make you feel better in the short term. If you cut them out cold turkey you can go through withdrawal which can bring on a wide variety of nasty symptoms, in my case I found that I was constantly thinking about the foods and how much I wanted to eat them, and the fact that I had to avoid them made me angry and depressed. Once you get past those first couple of days its smooth sailing though.

I beleived in that anti diary crap for a while but its just a big scam, just like the anti aspartame bull****.
I am personally convinced that its the healthiest to go on a low carb diet, i cant do it myself tough, havent got the willpower.

[Jimminy_Billy_Bob]

Actually its very real, particularly gluten brain allergies, not so much dairy. I'm not saying everyone is sensitive, but I know for sure that I am and always have been. Just something for people to try if they are short on drug treatment options.