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Grandaxin (tofisopam)?

Y

yaesutom

Bluelighter
Joined
Oct 15, 2000
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I've never heard of this drug before, has anyone else? I guess its been used in other countries for quite a while.

Grandaxin (tofisopam)
Grandaxin relieves various symptoms caused by tension imbalances
between the sympathetic and parasympathetic nervous systems. It
has proved effective in treating a variety of stress-induced ailments.
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From http://www.velapharm.com/news/press020614a.html ,

VelaPharm Advances Development of Tofisopam for the Treatment of Anxiety in the U.S.
Preclinical Data Presented at NCDEU, a National Institute of Mental Health Conference in Boca Raton

Lawrenceville, NJ (June 14, 2002) - Vela Pharmaceuticals (www.velapharm.com), a privately held pharmaceutical company specializing in the development of medicines for the central nervous system, presented preclinical data this week on tofisopam at the National Institute of Mental Health/New Clinical Drug Evaluation Unit (NCDEU) General Meeting in Boca Raton, Florida.

Tofisopam, an anti-anxiety agent first approved over 25 years ago and currently marketed in more than 15 countries, has a benign safety profile and a broad spectrum of clinical activity, including effects on anxiety, depression, autonomic dysfunction, IBS, and perimenopausal symptoms. In addition, tofisopam, a racemic 2,3-benzodiazepine comprised of R- and S-enantiomers, is unlike traditional 1,4-benzodiazepines, as it appears to be nonsedating, with minimal abuse liability and minimal cognitive impairment.
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Clinical Observations

Although tofisopam is a clinically effective anxiolytic agent with a chemical structure similar to that of the typical benzodiazepines, its binding profile is clearly distinct from that of any known 1,4- or 1,5-benzodiazepine receptor agonist.

In addition, unlike typical benzodiazepines, tofisopam was inactive in a conventional animal model of anxiety, the elevated plus-maze test. However, the drug was active in the water-immersion stress test. This activity, consistent with an anxiolytic effect, suggests a mechanism of action that may involve stress pathways. These data indicate tofisopam has a unique preclinical neurochemical and behavioral profile, one that is clearly distinct from that of typical benzodiazepines.
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Nah, I can't find any binding data, but it's probably just a subtype selective GABA-A modulator... or it's got inverse agonism at certain subtypes... like Ro 15-4513 or something.
 
I've used it in Korea, for control of anxiety, took twice a day, low dose. Very good for lowering number of anxiety-type attacks. No sedation, no side effects at all. Does anyone know what other countries it's available in, as I don't live in Korea any more...?
 
"Tofisopam is not approved for sale in the United States or Canada. However, Vela Pharmaceuticals of New Jersey is developing the D- enantiomer (dextofisopam) as a treatment for irritable bowel syndrome." Wikipedia

http://en.wikipedia.org/wiki/Tofisopam

^Are normal benzo's useful in IBS - anyone know?
 
It is a Benzodiazepine, with all the properties of Benzos (anxiolytic, sedative, muscle-relaxant, anticonvuslant), and some other properties: Inotropic and Coronary Vasodilator.

www.psychotropics.dk says:
Used in the treatment of neurotic and anxious-depressive disorders. Also as premedication and for sleep induction. Dosage 75 to 300mg/day. Mean plasma half-life 1. 4 hours.
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It is commercialized in Hungary, Slovakia and Portugal as "Grandaxin" by Egis.
It was commercialized in France as "Grandaxine" and "Seriel" (50mg tabs).


Here's the Inchem page of Tofisopam:
http://www.inchem.org/documents/pims/pharm/pim686.htm

Here's a long thread about it:
http://www.bluelight.ru/vb/showthread.php?t=298873&highlight=tofisopam
The thread is called " a benzo that reduces anxiety and increases energy motivation, it exists!"
and it says:
"it possesses anxiolytic properties but not anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing or amnestic properties"
 
Tofisopam does not bind in the CNS and neither to the 1,4-benzodiazepine, nor to the GABA receptors, but it enhances the binding of benzodiazepines and muscimol to their binding sites. Tofisopam has also mixed dopamine agonist and antagonist like properties


Any drug capable of blocking dopamine receptors is capable of inducing parkinson's and other dysfunctions. Even minute quantities of such a drug can easily damage you for life. But I'm sure the someone here will get the picture once they try it.
 
^^
Yup, I tried olanzapine once and the effects were frightening... Nothing to mess around with.
 
Parkinsonism is the best comparison for EPS (extrapyramidal symptoms), but there are distinctions. A lesion of the substantia nigra compacta (Parkinsons), and an all-over-the-map blockade of D2 in the nigrostriatal pathway (neuroleptics) are still probably as similar to eachother as a chemical blockade and a lesion could be.

I've never quite understood whether tardive dyskinesia (the motor symptoms that last way past cessation) is caused by receptor density regulation/changes in gene expression, and whether it is actually distinct from the EPS (and even the acute neurolepsis). They list different symptoms (eg for TD - tounge protrusions, vacuous chewing), but never describe why they are distinct in method of action
 
extrapyramidal symptoms is just another term for tardive dyskinesia according to what I managed to find.
 
No, EPS is a temporary side effect caused phenothiazines that ceases when the med is discontinued. whereas Tardive Dyskinesia is an often permanent disorder that is also caused by phenothiazines. They have similar symptoms, but they are indeed different problems. There is evidence that people who experience EPS are more likely to get Tardive Dyskinesia.
 
CH3CH2OH said:
No, EPS is a temporary side effect caused phenothiazines that ceases when the med is discontinued. whereas Tardive Dyskinesia is an often permanent disorder that is also caused by phenothiazines. They have similar symptoms, but they are indeed different problems. There is evidence that people who experience EPS are more likely to get Tardive Dyskinesia.
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just evidence? I thought it was pretty clear now, no?

---

Anyway, I wanted to ask a question about this because I can't find a good answer.

Earlier in this thread it's said that Tofisopam doesn't bind in the CNS, but AFAIK it definitely does.

I found a paper that described these 2,3-benzos as AMPA antagonists (in: 2,3-Benzodiazepines (GYKI 52466 and Analogs): Negative Allosteric Modulators of AMPA Receptors

* E. S. Vizi11Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.,
* A. Mike11Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. and
* I. Tarnawa*)

Is this what causes the stimulation?

Another paper I saw also briefly described some sort of effect on mu-opioid receptors, and another one mentioned it's potential use as a mood brightener by somehow affecting endorphin levels or their affinity, or something I can't even begin to grapse.

On the first page it's also said that it's a dopamine agonist, but I can't find anything confirming that.
 
I put evidence because it is not sure sign that someone will develop Tardive Dyskinesia if they get EPS, but they do have higher chances of developing Tardive Dyskinesia if they are prone to EPS reactions. But Tardive Dyskinesia does not require that someone has had EPS symptoms in the past and can occur on the first dose and be permanent. You are right though, there is certainly a proven correlation between the two.

They cause some nasty problems, this is why I really do not like the frequency w/ which Dr's prescribe phenothiazine anti-emetics like Phenergan and metoclopramide (Reglan) without telling the patient anything about the possibility of EPS or Tardive Dyskinesia (though i can see not mentioning Tardive Dyskinesia as it would scare away many patients and is very rare in these weak phenothiazines), but I can only imagine how horrified I would be if I took a dose of my Codiene/Phenergan cough-syrup and started to have EPS. I suppose your average joe would go to the ER (if they had insurance).

By the way, I have experienced EPS, both from Compazine and Metoclopramide, and it is EXTREMELY uncomfortable, worse, IMO, than severe pain. As in if I had to choose to experience either EPS or level 8-9 pain (on the 1-10 pain scale) for the rest of my life, I would choose the pain. I have also experienced pain of that level, I was hospitalized for it, though i know it is a very subjective scale.

I know that that last bit is somewhat off-topic, sorry, just saying that Dr's prescribe those meds like there are no risks and without telling patients about them, but they have some really nasty side-effects. And EPS can simply be remedied with benadryl, if the Dr's took the time to inform the patients of this it would save the patients who get EPS from those meds a lot of discomfort.
 
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