What is the most toxic barbiturate?

[Flynnal]

Hey guys,

I've been pondering about this for a long time. I've read various documentation on barbiturates, but never anything that would give me any reasonable conclusion as to what is the most toxic of the barbiturates.

If I were to take a wild guess, the most toxic barbiturate that was ever synthesized and commercially available would be pentobarbital. But I do believe there are other examples that may be even more toxic.
Another interesting question would be the opposite - that being what is the least toxic of the barbiturates. I've heard it on good authority that cyclobarbital is probably the least toxic, but that may be wrong.

Does anybody have any more information who can provide an authoritative answer? It's something that has fascinated me for a long time. This is the only group of drugs for which I have the least amount of knowledge at hand. For the most part I know a great deal about most drug classes, except barbiturates.

If anyone can chime in and provide some answers that would be great.

 

[sekio]

I think the LD50 of barbs is correlated directly with their potency; that said that means that something like secobarbital or sodium thiopental probably takes the cake.

You should probably define "toxic" a little better, if you are worried about non-respiratory-depressant effects.

 

[dingophone]

I think the LD50 of barbs is correlated directly with their potency; that said that means that something like secobarbital or sodium thiopental probably takes the cake.

You should probably define "toxic" a little better, if you are worried about non-respiratory-depressant effects.

Yeah, I've read that thiopental, secobarbital, and hexabarbital are the most deadly. As far as negative side effects go, pentobarbital is famous for being incredibly unpleasant, barbital has a ton of nasty problems (ie putting people to sleep for days), and butalbital (apparently, not 100% sure of this one) is supposed to be kind of unpleasant too.

No idea what the safest would be, hopefully someone can answer it?

 

[Flynnal]

Seeing that barbiturates can either be depressants or convulsants, it is the depressant toxicity that I was interested in. I know there are some incredibly toxic barbiturate convulsants that typically use a 3,3-dimethyl substitution at the C-3 position.

I was told hexobarbital was less toxic than pentobarbital, and that secobarbital was less toxic than hexobarbital, putting it third. Thiopental, I'm told, is not all that toxic since it is eliminated from the system too quickly for it to accumulate but that could be a mistaken assertion. I was also told that sodium Amytal (amobarbital) was just as toxic as secobarbital, just that it's onset of action and peak accumulation in blood/CNS took longer, but then someone else claims that it is much weaker than secobarbital and couldn't possibly be as toxic.

But I'm still not entirely sure. I know for certain that pentobarbital is used for veterinary euthanasia and anaesthesia. I don't understand why it would be famous for being so unpleasant, if it was that unpleasant then vets wouldn't use it to anesthetize animals or to put them to sleep. Is that pentobarbital or phenobarbital you are referring to? One is short acting the other is long acting. I would understand if it was phenobarbital since it uses an aryl group as one of it's substituents.

I suppose going by reputation alone, it would be pentobarbital. That could well be wrong, but I have nothing else of reference to go on. There was another barbiturate known as Evanal Sodium going back to 1987 in one of the European bloc countries, which is almost identical to Seconal, the only difference being that the second side chain has a double bond instead of the single bond at the secondary butyl (1-methylbutyl) position.

 

[Flynnal]

No idea what the safest would be, hopefully someone can answer it?

I had it on good authority that it was methohexital, which ironically is the most potent of the depressant-type barbiturates. Now that is strange...which seems to point out that potency and toxicity are not mutually inclusive.

 

[Pomzazed]

Is not the OP's name the most toxic one? (Flynnalbarbital)

 

[endotropic]

There's two legitimate ways you could categorize barb's by toxicity:

You could find the drug that will poison you at the absolute lowest amount of drug (i.e. lowest TD50, lowest dose that produces the toxicity in 50% of people)

Or you could find the drug with the smallest separation in dose between the desired effect, and the toxic effect (i.e. the therapeutic index)

The most toxic drug is going to depend on which of these definitions you want to use.

 

[dingophone]

Seeing that barbiturates can either be depressants or convulsants, it is the depressant toxicity that I was interested in. I know there are some incredibly toxic barbiturate convulsants that typically use a 3,3-dimethyl substitution at the C-3 position.

I was told hexobarbital was less toxic than pentobarbital, and that secobarbital was less toxic than hexobarbital, putting it third. Thiopental, I'm told, is not all that toxic since it is eliminated from the system too quickly for it to accumulate but that could be a mistaken assertion. I was also told that sodium Amytal (amobarbital) was just as toxic as secobarbital, just that it's onset of action and peak accumulation in blood/CNS took longer, but then someone else claims that it is much weaker than secobarbital and couldn't possibly be as toxic.

But I'm still not entirely sure. I know for certain that pentobarbital is used for veterinary euthanasia and anaesthesia. I don't understand why it would be famous for being so unpleasant, if it was that unpleasant then vets wouldn't use it to anesthetize animals or to put them to sleep. Is that pentobarbital or phenobarbital you are referring to? One is short acting the other is long acting. I would understand if it was phenobarbital since it uses an aryl group as one of it's substituents.

I suppose going by reputation alone, it would be pentobarbital. That could well be wrong, but I have nothing else of reference to go on. There was another barbiturate known as Evanal Sodium going back to 1987 in one of the European bloc countries, which is almost identical to Seconal, the only difference being that the second side chain has a double bond instead of the single bond at the secondary butyl (1-methylbutyl) position.

Interesting, I've honestly not heard much about pentobarbital in general. Was it just not used as much as amobarbital and secobarbital? Anyways, definitely meant phenobarbital there! AFAIK it's LD50 isn't especially noteworthy compared to other barbs, but the number of side effects associated with it is certainly something to consider.

What you're saying about thiopental makes sense, but I've read in a few places that the acute toxicity is much higher for it than most other barbiturates. Hexabarbital, like barbital, is known for having a wildly unpredictable dose-response curve, but it's significantly stronger, so there was obviously more danger in using it. It wasn't used in anesthesia for very long for this exact reason.