19 replies to this topic

[jakord]

I wondered why there is so little mention on tofisopam, as it is one of the drugs that just sounds to good to be true and is easily to find online here in europe: http://en.wikipedia.org/wiki/Tofisopam

It's structurally a benzodiazepine, but its mode of action is very different from benzos. It doesn't act on gaba, though it's claimed to have anxiolytic effects without any sedation and it is said to be free of any withdrawal.

I think I read all the experience report on the net, and it seems like although Tofisopam has no recreational value, it is good for people suffering from anxiety disorders like GAD.

Anyone have any experience with it?

Edited by morpheus1990, 20 April 2013 - 03:27 PM.

[BioInfinite]

This is a very interesting anxiolytic, the term atypical benzodiazepine was coined for this drug as it has zero affinity for GABA receptors, rather it is a PDE-4 and PDE-10 inhibitor most significantly, and has also shown antipsychotic and antidepressive potential.

There is a study that has much better info than the wikipedia article:

"The atypical anxiolytic drug, tofisopam, selectively blocks
phosphodiesterase isoenzymes and is active in the mouse
model of negative symptoms of psychosis"

by Chris Rundfeldt •
Katarzyna Socała •
Piotr Wlaz

I have never tried it myself, but it certainly looks like a great alternative to GABA-ergics.

Edited by BioInfinite, 22 April 2013 - 05:25 PM.

[nowayout]

What would be its principle of action, hypothetically?

[jakord]

What would be its principle of action, hypothetically?

Furthermore, the additional inhibition of PDE-2 may also contribute to the overall activity, adding anxiolytic effects and potentially also positive effects on cognitive function.

http://www.ncbi.nlm....pubmed/18456873 (Reversal of oxidative stress-induced anxiety by inhibition of phosphodiesterase-2 in mice)

Tofisopam, a 2,3-benzodiazepine, has been shown to have anxiolytic activity. However, in contrast to the widely used 1,4-benzodiazepines, it has no anticonvulsant, sedative or muscle relaxant effects. Tofisopam enhanced the behavioural actions of various dopaminergic drugs, both direct agonists, such as apomorphine (climbing behaviour in mice), and indirect agonists, such as (+)-amphetamine and amineptine (jumping behaviour in mice). Chronic treatment with lithium abolished the tofisopam-induced increase in the activity of these dopaminergic drugs. Thus tofisopam appears to induce acutely an increase in the sensitivity of central dopaminergic receptors which can be prevented by pretreatment with lithium.

So it seems to upregulate dopamine receptors?



I think I'll give it a try. 300mg cost about 2,50€ per day, that's okay.

Edited by morpheus1990, 22 April 2013 - 10:10 PM.

[formergenius]

I was just doing some research into Tofisopam. Damn, I'd love to try this stuff.
However, it seems there's dopamine agonism and antagonism.. Someone from another forum commented that this could be detrimental to DA functioning, and eventually could lead to Parkinson's (allthough that is perhaps going a bit to far). Wonder what thoughts others have on this?

I'm very eager to hear of your experience, please do keep us posted! The stuff seems dirtcheap from the source I would buy it from (1g for $10.40).

[Dinvestor]

Yeah, I've wondered about this one too. Sure doesn't seem to get the love for all it's reported therapeutic effects and lack of bad stuff like withdrawal and tolerance, etc...

[niner]

An early paper:

Neurosci Biobehav Rev. 1986 Summer;10(2):221-7.
Is tofisopam an atypical anxiolytic?
Pellow S, File SE.

This review describes the behavioural and biochemical profile of tofisopam, a 3,4-benzodiazepine that differs considerably in its effects and mechanisms of action from classical 1,4-benzodiazepines. In man tofisopam appears to possess anxiolytic activity without appreciable sedative and muscle relaxant side effects; in animals, however, tofisopam totally lacks anxiolytic and anticonvulsant properties in tests sensitive to the effects of 1,4-benzodiazepines. Tofisopam also has mixed dopamine agonist and antagonist-like properties in several in vivo and in vitro tests in animals. The possible relevance of the latter effects to the unusual behavioural profile of tofisopam are discussed, and its effects compared with those of buspirone, a novel anxiolytic that has similar activity at benzodiazepine and dopamine systems. It is proposed that these two drugs may represent a novel class of compounds that reduce anxiety by increasing the ability of patients to cope with daily tasks, rather than classical anxiolytics, that reduce anxiety by tranquilization.

PMID: 2874535

Hmm. What do you make of this?

[formergenius]

An early paper:

Neurosci Biobehav Rev. 1986 Summer;10(2):221-7.
The possible relevance of the latter effects to the unusual behavioural profile of tofisopam are discussed, and its effects compared with those of buspirone, a novel anxiolytic that has similar activity at benzodiazepine and dopamine systems. It is proposed that these two drugs may represent a novel class of compounds that reduce anxiety by increasing the ability of patients to cope with daily tasks, rather than classical anxiolytics, that reduce anxiety by tranquilization.

PMID: 2874535

Hmm. What do you make of this?

Double use of novel in two consecutive sentences?

Hmm, do you smell conflict of interests? And indeed, "increasing the ability to cope with daily tasks" is also rather vague.

[socialpiranha]

Currently retrying this drug, tried it once and had some strange sensations around my heart similar to other phosphodiesterase inhibitors so i stopped. I am less paranoid about my heart failing lately so giving it a try at a higher dosage.i'll report back

[jakord]

I've tried tofisopam, and like it so far. It's not a wonder drug, but it's by far the best non-addictive anxiolytic I've tried so far. It dosen't feel like normal benzos, there is no recreational value. You might compare it to modafinil: Modafinil has the wake-promoting properties amphetamine has, minus the fun. Tofisopam has a nice anxiolytic effect minus all the fun gabaerics provide. I really wonder why it is not a more widely used medication.

Edited by morpheus1990, 05 July 2013 - 11:03 AM.

[socialpiranha]

I'm kind of curious as to why it's so unknown too, it definitely has therapeutic potential. I have a feeling it could be extremely beneficial for paranoia and delusions in schizophrenia/bipolar. It seems to very slightly change the speed and content of the thought process. It also feels a bit like a neuroleptic though in higher doses and can be slightly dysphoric, cognitively dulling and could possibly cause extrapyramidals eventually because of it's dopaminergic effects.

The stimulant action could be very beneficial for someone who is asthenic or depressed yet is not prone to anxiety. The best way i can describe it is, it is physically anxiogenic yet mentally anxiolytic. Haven't tried it with a classic benzo or beta blocker yet but i'm guessing they would synergize very well.

[jakord]

I'm kind of curious as to why it's so unknown too, it definitely has therapeutic potential. I have a feeling it could be extremely beneficial for paranoia and delusions in schizophrenia/bipolar. It seems to very slightly change the speed and content of the thought process. It also feels a bit like a neuroleptic though in higher doses and can be slightly dysphoric, cognitively dulling and could possibly cause extrapyramidals eventually because of it's dopaminergic effects.

The stimulant action could be very beneficial for someone who is asthenic or depressed yet is not prone to anxiety. The best way i can describe it is, it is physically anxiogenic yet mentally anxiolytic. Haven't tried it with a classic benzo or beta blocker yet but i'm guessing they would synergize very well.

What doses do you take to make it feel neuroleptic? It's weird it feels physically anxiogenic for you, as in some study they say "The drug was especially effective in the treatment of somatic difficulties." For me, there isn't any real physical effect.

[aardvark82]

I've used Grandaxin for a few years. It dramatically reduced my permanent anxiety after 1-2 months of usage, no obsessive "scary" minds before going sleep and so on. I take it now from time to time (2 pills) in case of heavy stress...

Bad effects - Grandaxin causes moderate headache it the beginning of treatment, and it causes annoyance and aggressiveness after long-term usage (funny - just like "energy" drinks or large amounts of coffee or tea).

I've also tried another no-addiction-no-tolerance anxyolytic drug Atarax. Pretty good as tranquilizer, but it may cause insane sleepiness and weakness. The worst thing about it - it causes sleepiness in RANDOM time after taking pills. You take it at 10 p.m. to help to sleep, you sleep as usually, and at 11 a.m. (or 2 p.m., or 10 a.m., or any other time) next day you want just to fall down and SLEEP F**KING RIGHT NOW

[xks201]

Got a source for it?

[mrd1]

" that reduce anxiety by increasing the ability of patients to cope with daily tasks, rather than classical anxiolytics, that reduce anxiety by tranquilization."

-LOLOLOL! That put me in a good mood. - In a despite attempt to bring this back to science -

So, this is a

PDE2, PDE4, and PDE10 Inhibitor? Has a role on the dopamine system? sensitivity? Upregulation? Any specifics on the subtpyes D1...D7???

Is perhaps one of the reasons it is not more popular because of its inihibition at the CYP3A4 enyzme? (PMID 16711396)

As for the PDE4 inhibition what about Mesembrine? However, it appears to be a weak inhibitor I do not know if that is strong enough.

Maybe Papaverine as a PDE10 inhibitor although it is interesting that when administered chronically to rats it produced cognitive deficits and increased anxiety? "Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis"

If PDE10 inhibition was the cause of this chemicals antianxiety effects doesn't this seem to provide evidence against that hypothesis ?


What about nonselective but easily available pohosphodiesterase inhibitors

Caffeine
Parxanthine
theobromine

-Side note- maybe if sensitive to caffeine we could make our own mix of xanthines that doesn't include caffeine??-

Lastly, does anyone know how lithium can go about preventing the increased senstivity to dopamine agonists.

[capatt]

I see this is an old thread, but I recently began researching this compound.  I don't have much time, but I do want to say it's wonderful.  Thirty minutes after the first time I took it, the entire universe seemed to say, "Ahhhhhhh....".  

 

I'm stocking up.

 

Insomnia is the only drawback, so take it early in the day.  I think the abuse potential is low as it doesn't drive you to redose.  It's good as needed.

[Soma]

It also feels a bit like a neuroleptic though in higher doses and can be slightly dysphoric, cognitively dulling and could possibly cause extrapyramidals eventually because of it's dopaminergic effects.

Extrapyramidals?

Is this not essentially synonymous with, or at least related to, tardive dyskinesia?

If this drug does have this dopaminergic mechanism, one might want to tread carefully should they develop what happens to be one of the most torturous and unsightly of any side effect- tardive dyskinesia. Essentially permanent lizard tongue.

If you've never witnessed this, there are probably videos online. Quite horrific. Suicide is not uncommon in permanent cases.

[aardvark82]

I've recently tried "real" 1,4-benzo, phenazepam. F**k this s**t, I hate it. Where Grandaxin really cures fears, tension, anxiety and just makes everything "OK as it should be" phenazepam just makes you DRUNK. You can achieve same "anxiolytic" properties from glass of whiskey, not from tranq pills.

 

The most coolest thing about phenazepam, whan taked with alcohol (two beers in my case) it causes poisoning, vomiting and HALLUCINATIONS - I've really saw twiced peoples, things and so on.

 

Grandaxin rulez!

[Ron.Stone]

I'm using Tofisopam for schizophrenia. I combine it with amisulpride. It helps. A few minutes after i take 100mg Tofisopam i recognize a difference in acoustic perception. It's slight but it's everytime the same thing. My question is: Does it make sense to combine Tofisopam with e.g. Rasagiline, a MAO-B inhibitor to push the effects of the former one? 

Edited by Ron.Stone, 25 August 2018 - 02:04 AM.

[John250]

Where did you guys order it?