How not to use clobazam

[Fertile]

Clobazam represents the safest benzodiazepine by a HUGE margin. The reason being that 100% occupancy of the GABA receptor site it binds to does not lead to one passing out, forgetting what one is doing or doing crazy/stupid/illegal stuff - just just LIE DOWN. Even 100 pills won't cause toxicity or the usual side-effects of benzo overdose.

But the tablets contain the FREEBASE of clonzepam, so nothing but swallowing it works. Snorting/shooting/smoking are OUT.

I've noted it's now being used in the US and predict it replacing all of the other benzos used as anxiolytics.

BUT here is the danger. All other benzos are technically 1,4-benzodiazepines. One will happily replace another in people who are dependent on benzos.

But clobazam is a 1,5-benzodiazepine. So it will NOT stop benzo withdrawal (unless you are dependent on clobazam) and it has an upper limit. More than 40mg doesn't do any more. So you can SEE why US physicians are so keen.

Just don't buy clobazam because you have a diazepam rattle.... it will help a BIT, but that is all.

But above all - don't snort the pills. Nasty and bioavailability seems low. Also painful.

 

[izo]

But the tablets contain the FREEBASE of clonzepam

how is there a freebase of clobazam if there isnt any amine? you cant make salts out of the imines. there is the imine n-oxide like in librium thats it, right?

had 10mg of clobazam once, was exactely like diaz.

 

[Fertile]

Well imines will form salts and don't forget, drugs with acidic moieties form addition salts with based - chlorazepate potassium, for example,
No, both nitrogens in clobazam are amides. There are no imines. I was pointing out that it couldn't form addition salts, if you read the post properly.

A subjective experience in 1 person isn't a fact and while clobazam is similar, it binds to different sites and it has a ceiling - more than about 40mg does no more. It isn't cross-tolerant and someone with a dependence on any other benzo will find clobazam of little to no help. I mean, it IS sedating, so it helps a bit, but it's really not much use.

 

[izo]

A subjective experience in 1 person isn't a fact and while clobazam is similar, it binds to different sites and it has a ceiling - more than about 40mg does no more.

first one goes without saying:

the plural of anecdote is not data.

didnt knew about the second part though.

 

[Fertile]

The ceiling off effects is recorded - by Dr. Ashfield, for a start.

 

[emkee_reinvented]

Do you know the binding affinities?

Pyrazolam is selective for a2 and a3 subunits. And is also is a a-typical Benzo.

 

[Fertile]

I don't - without the LogP & pKa data, affinity will only tell you how it binds to receptors in a culture, not in the human body.

 

[emkee_reinvented]

I don't - without the LogP & pKa data, affinity will only tell you how it binds to receptors in a culture, not in the human body.

LogP and pKa are two terms I have to look up and read into. No clue what that refers to and what the consequence for Clobazam vs other Benzo's is.

I did see that Clobazam has
"higher affinity for α2 containing receptors, where it has positive modulatory activity"
https://en.wikipedia.org/wiki/Clobazam
Like Pyrazolam. But less for the α1 receptor (unlike Pyrazolam), these are responseable for sedation and hypnotic effects of Benzodiazepinen.

My own experience is that its indeed not really sedative. And its slow come up and decline are a plus to when used medically. as it doesn't interfere with your daily live as other Benzo's do. Excluding Pyrazolam which also seems to lack sedation.

On https://pubchem.ncbi.nlm.nih.gov/compound/Clobazam#section=Vapor-Pressure
The XlogP 3 of Clobazam is 2.12. LogP is the octanol–water partition coefficient and is used to adduce how a drug molecule partitions itself into the lipid surroundings of the receptor microenvironment. That's beyond my scope btw but thought i'd post it anyway.
https://www.sciencedirect.com/topics/chemistry/logp

On pKa's, which i find even more vague. "pKa is a number that shows how weak or strong an acid is."
https://chemistrytalk.org/what-is-pka/
Interesting but I have again not the slightest idea what this means in relation to Clobazam. I feel like a Noob.

 

[Fertile]

Lofendazepam, afendazepam, triflubazam and CP-1414S help to divine the QSAR of the 1,5-benzodiazepine class. It's worth noting that they are all prodrugs. I've never seen a '2-substituent so suggest that it's not a fruitful area of research.

It's worth noting that the triazolo derivatives of various 1,5-benzodiazepines have been prepared.

https://ibb.co/QF3g92C

I don't know if animal models have been tested but it does open up an entirely new class of RC. Clobazam is only 1/2 the potency of diazepam but IF clobazolam shows the same potency increase as diazepam -> alprazolam, it would be pretty potent. Of course the triazolo class generally has a shorter T1/2 than the simple 4-ring benzodiazepines so clobazam might be chosen because it only requires BID administration.

 

[emkee_reinvented]

Lofendazepam, afendazepam, triflubazam and CP-1414S help to divine the QSAR of the 1,5-benzodiazepine class. It's worth noting that they are all prodrugs. I've never seen a '2-substituent so suggest that it's not a fruitful area of research.

It's worth noting that the triazolo derivatives of various 1,5-benzodiazepines have been prepared.

https://ibb.co/QF3g92C

I don't know if animal models have been tested but it does open up an entirely new class of RC. Clobazam is only 1/2 the potency of diazepam but IF clobazolam shows the same potency increase as diazepam -> alprazolam, it would be pretty potent. Of course the triazolo class generally has a shorter T1/2 than the simple 4-ring benzodiazepines so clobazam might be chosen because it only requires BID administration.

It isn´t Clobazam is about as potent as Diazepam 10 mg. Only less sedating. Nothing like Alprazolam which is active at 0.5mg and guite sedating.

Gonna check out your link and look up what BID means. Not a abbreviation I know off what it means. But my Clobazam is prescripted for prevention of a seizure. And for that it works like a charm. Unlike Oxazepam which I received as replacement recently. Clobazam shortages.

 

[Fertile]

The Asdton Manual lists equipotency data. 20mg of clobazam is listed as equating 10mg of diazepam.

I've been prescribed clobazam for decades and yes, initially it is a little sedating but less so than diazepam. I think it's because it's a 1,5-benzodiazepine so it binds to a different subset of GABA receptors than other benzodiazepines.

I've never tried it but people tell me that mixing diazepam and clobazam has a much more profound effect. I wouldn't, who knows what it's going to do.

Etifoxine is another related medicine. It's prescribed for anxiety in France.

 

[Delmonte421]

Clobazam represents the safest benzodiazepine by a HUGE margin. The reason being that 100% occupancy of the GABA receptor site it binds to does not lead to one passing out, forgetting what one is doing or doing crazy/stupid/illegal stuff - just just LIE DOWN. Even 100 pills won't cause toxicity or the usual side-effects of benzo overdose.

But the tablets contain the FREEBASE of clonzepam, so nothing but swallowing it works. Snorting/shooting/smoking are OUT.

I've noted it's now being used in the US and predict it replacing all of the other benzos used as anxiolytics.

BUT here is the danger. All other benzos are technically 1,4-benzodiazepines. One will happily replace another in people who are dependent on benzos.

But clobazam is a 1,5-benzodiazepine. So it will NOT stop benzo withdrawal (unless you are dependent on clobazam) and it has an upper limit. More than 40mg doesn't do any more. So you can SEE why US physicians are so keen.

Just don't buy clobazam because you have a diazepam rattle.... it will help a BIT, but that is all.

But above all - don't snort the pills. Nasty and bioavailability seems low. Also painful.

The 1,4-benzodiazepines have a recognised place in the treatment of epilepsy. Thus, diazepam, clonazepam, and, more recently, lorazepam are used intravenously for status epilepticus. Oral clonazepam has proved useful as adjunctive therapy in generalised absence seizures, myoclonic seizures, and partial seizures. Oral nitrazepam is well known for its use in the treatment of infantile spasms with hypsarrythmia and in the myoclonic epilepsies of childhood. Clobazam, a 1,5-benzodiazepine, has been shown in controlled studies to be superior to placebo, and in open studies it has produced an overall reduction in seizure frequency of 65%. The main indication for its use is as oral adjunctive therapy in refractory epilepsy. It has a rapid onset of action, is well tolerated, and many studies indicate it has a psychotropic action and produces minimal or no cognitive impairment. The most common side-effect reported was sedation, while the overall incidence of side-effects in the open studies was 38%. In all studies reviewed, 4% of patients had to be withdrawn because of adverse reactions. In general, there are no significant interactions with other anticonvulsants, although changes in a few have been described. Withdrawal seizures can occur and require gradual termination of clobazam. The main disadvantage of clobazam is the development of tolerance, which develops in approximately 36% of patients, and there is no way of predicting in which patients or when the phenomenon is likely to occur. A dose of 20 to 30 mg at night is recommended, possibly commencing at 10 mg.

 

[Fertile]

I would agree with the above based on reading other technical data and then from personal experience. It will produce tolerance (to sedating effects) quickly but I had to take it for over a year before I had any kind of dependence. That was minor when compared to 1,4-benzodiazepines. Just felt edgy and didn't sleep well for a few days.

It CAN be useful for the short-term treatment of anxiety and it seems to be as effective as etifoxine. Neither of them will directly treat dependence on 1,4-benzodiazepines BUT since they are anxiolytics in their own right, may be of value as 'comfort medications'.