[The_rationalist]

No, your answer makes sense but your are being fooled. Tofisopam is not a benzodiazepine. It is what we call a 2,3 benzodiazepine. This is an exception that makes it radically different than any other benzo. It does not directly bind at GABA-A like e.g klonopin and is a weaker anxyolitic. It's action mechanisms is very atypical, it acts as a PDE inhibitor, as a GABA PAM and as a dopamine presynaptic antagonist, making it mildly stimulant. The effect on phopshodiesterases give it unique pharmacology including neuroprotective effects.

Therefore this study shows effectiveness that is theoretically higher than regular benzos. I don't think that regular benzos or tofisopam block the AMPA receptors, although their increase in inhibitory GABA has a similar effect. It would make sense to combine benzos with an NMDA antagonist such as e.g memantine in order to reduce excitotoxicity (or weaker ones like magnesium l-threonate)

I advise you to try tofisopam (grandaxin) especially since it is a safe and extensively studied drug. Tofisopam is for sale in the U.S, OTC in practice e.g on rupharma, cosmicnootropics, possibly indiamart, etc You should not take it in combination with klonopin nor any other drug without advice from an expert (spoiler almost no-one is qualified) as interactions are possible. E.g it is a CYP inhibitor like grappefruit juice. note that the dose escalation must be very slow since tofisopam slightly increase heart contractility which can give non-dangerous but scary transient heart palpitations for a limited subset of the population.

There are many interesting neuroprotectants/modulator e.g BPC-157, cerebrolysin, etc However the most promising treatment besides tofisopam, is a drug that is only available in japan: https://www.semanticscholar.org/paper/Effectiveness-of-Celep... It is likely that tinnitus is already a solved problem, but no one knows it yet besides a few retired scientists.

A complete pharmacological response would also look in synaptotrophics and in mitochondria targeted antioxidants, such as SkQ1

[FollowingTheDao]

Tofisopam is a type of benzodiazepine, yes? Benzodiazepines are depressants that enhance the effect of the GABA, and the literature suggests that tofisopam does not act on the GABA-A receptor but it does enhance the binding of other benzodiazepines to their binding sites.

Any increase in GABA will counteract the excitatory transmission of Glutamate. That is all that matters.

But I know klonopin can eliminate my Tinnitus. So if you can explain how that works go right ahead.

[The_rationalist]

> Any increase in GABA will counteract the excitatory transmission of Glutamate. That is all that matters. No that is not all that matters. The main effect of tofizopam is unrelated to GABAergy, the fact it indirectly modulate GABA-A and potentiate benzos is a plus but its main effect come from atypical PDE inhibition. Look if klonopin is viable for you and solve your tinnitus that's great to hear. But for many people regular benzos are not a complete solution. Tinnitus is a multi-factorial condition and some people might get better results that other with a given medication.

> if you can explain how that works go right ahead Tinnitus is an excitatory overload localized in audition related neuron circuits. AKA too much glutamate (mGLURs, AMPA, NMDA, kainate). The brain is mostly a mixture of excitation (GLUT) and inhibition (GABA-A, B). By taking a classical benzo like klonopin you increase your GABA-A level which inhibit the overload of excitation (GLUT). That is why it works. You can also lower you glutamate levels independently of you GABA via an NMDA antagonist such as memantine. Those two mechanisms are the basic treatments to tinnitus. However there are more specific mechanisms (PDE, synaptotophics, calcium blockers, anti oxidants, bioenergetics) that can be complementary. Classical benzos and NMDA antagonists are not enough for some people with tinnitus.

[FollowingTheDao]

> The main effect of tofizopam is unrelated to GABAergy

It's a antagonist of the AMPA receptor. I am not saying it has anything to do with GABA-A but it enhances the action of GABA.

https://www.nature.com/articles/nn0600_551

>By taking a classical benzo like klonopin you increase your GABA-A level which inhibit the overload of excitation (GLUT).

No, Klonopin does not increase GABA, it attaches to the GABA-A receptor to allow more chloride into the cell. It only enhances the activity go GABA.

https://en.wikipedia.org/wiki/Clonazepam#Pharmacology

[The_rationalist]

I have not found information saying that tofisopam is an AMPA antagonist. But you are probably right, the answer must be on the paper you link I guess. Nevertheless the action on PDEs is what makes tofisopam unique.

> No, Klonopin does not increase GABA Yeah that's right. GABA releasing agent, GABA reuptake inhibitor and GABA transaminase inhibitors do exists but benzos have not those properties. They are GABA-A positive allosteric modulators (they are not agonists although GABA agonists do exist too). So yeah they potentiate GABA functionally without increasing its quantity directly.

[philliphaydon]

I've never heard of this.. https://en.wikipedia.org/wiki/Fludiazepam

Is this the same? I'm in Taiwan so googling to figure out what i could ask the pharmacist for to try.