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Capsazepine

j.t.delaney

j.t.delaney

Hey there,

I've been often asked as a chemist, what is the best way to counteract an overdose of capsaicin. All the old-school 'remedies', like milk and starchy foods, are all effectively extraction techniques: the mode of action is to provide something lipophilic to absorb some of the spicy-spicy. This just isn't a satisfying solution, to my way of thinking at least. What is needed is a true, old-fashioned, down-home antidote -- something that will counteract capsaicin, and neutralize it in vivo. If capsaicin is a transient receptor potential cation channel subfamily V member 1 (TrpV1) agonist, then we need a TRPV1 antagonist.

So, what's out there?

The most famous one seems to be capsazepine (CAS 138977-28-3.) I've been reading up on this, going through the primary and secondary literature on the topic, but I haven't found yet the answers to my two burning (ahem) questions:
  • What would be an approximate effective dose for relief?
  • What sort of safety issues should be considered?

Does anybody ahve any insights into this? There are hundreds of articles on capsazepine; where should I start?

Cheers,

-J.T.Delaney
 
Very interesting topic and I agree that it could be very profitable if you indeed come up with a safe antidote. However, you will never find me purchasing that antidote. I LOVE the burn! :onfire: :crazy:
 
So far, I've found examples of capsazepine being used effectively as a pre-treatment to capsaicin exposure, but I'm still looking to see what post-treatment might do. Pre-treatment would be handy for some applications where you have some forewarning (e.g. fixing a hot pepper eating contest, getting ready for a confrontation with riot cops), but it's not quite the same as first aid for a situation where you inadvertantly discover that superhots are not friendly (well, at least you could have it ready as a suppository for the Second Burn.) :onfire:

Hmmm. There's a lot more reading to do.
 
queequeg152 said:
thats interesting, are there any examples of this you can cite?
Click to expand...

I was wondering if anybody'd notice that. To tell you the truth, it was the pictures last week from UC Davis of that inspired me to look into this in the first place. Thanks, Lt. John Pike, for reminding me that one person can make a difference (ya jerk.) :shame:

So, I've been focusing on sources involving epidermal administration, or at the very least, activity in the skin.

US Pat 6048855
Topical composition containing capsazepine

Pain
Volume 109, Issue 3, June 2004, Pages 284-290
doi:10.1016/j.pain.2004.01.038
Effects of TRPV1 receptor antagonists on stimulated iCGRP release from isolated skin of rats and TRPV1 mutant mice

Journal of Pharmacology and Experimental Therapeutics
10.1124/jpet.102.040675
Activation of Epidermal Vanilloid Receptor-1 Induces Release of Proinflammatory Mediators in Human Keratinocytes

European Journal of Pharmacology
Volume 249, Issue 2, 9 November 1993, Pages 185-190
doi:10.1016/0014-2999(93)90431-G
Topical capsaicin administration protects against trinitrobenzene sulfonic acid-induced colitis in the rat
 
Most burns go away in 30 minutes mostly, many are way shorter.
Also most folks eating hot stuff know what they are getting into,
and they are self induced so to speak.

Just wondering aloud do "we" as in "consumers" really need another
over the counter(OTC) medication for something that nature will take care of
in a very short time once it(the burn) begins with? Especially when most
burns are self induced?


Coming at this conversation from the point/side that America has waaaaay to
many medications and OTC items to begin with. More than the rest of the
the world combined... which contrary to what the drug industry greed wants, is NOT a good thing.
I can appreciate that you are a professional chemist, but still... just because you "can"
create something, is it really needed for such limited usages. I personally think not.

One day history will look at the drug crazed society the west has become,
our impulse to chase EVERYTHING with a pill, and how public opinion about medicine
was so easily swayed by slick pharmacological marketing commercials and scoff at it.

Oh wait... it already has.
 
A self-inflicted pepper overdose is something I think most people can handle by just riding it out -- that's been exactly what people have been doing for over 5000 years. That isn't really a problem needing fixing. As fun and enjoyable as this forum is, I don't think there's any likelihood that any product with an API requiring FDA approval is going to be launched as a result of a discussion here. ;)

There is an enormous amount of research using capsazepine . Why? Because its a very convenient and selective antagonist for a very important receptor type in mammals, and its s fantastic probe for understanding how our nervous system functions.

On the other hand, non-self-inflicted capsaicin overdosing is a very different issue. Pepper spray and the way its being used on my fellow countrymen in recent weeks has left me with a sick feeling in my stomach. I'm interested in looking into what can be done to neutralize something I see as a very dangerous and destructive policy. I feel it's my civic duty as a scientist to do what I can.
 
That's a very interesting quandary. I would suggest you go to your nearest university and seek out a reference librarian. They are information super-slueths. If the info you seek is out there, they will find it. Especially if it is peer reviewed/scholarly research you are looking for.
 
j.t.delaney said:
On the other hand, non-self-inflicted capsaicin overdosing is a very different issue. Pepper spray and the way its being used on my fellow countrymen in recent weeks has left me with a sick feeling in my stomach. I'm interested in looking into what can be done to neutralize something I see as a very dangerous and destructive policy. I feel it's my civic duty as a scientist to do what I can.
Click to expand...


Fair enough. I agree, some recent scenes of spray being used on protesters has been quite out of hand, and I do see how they would benefit from what you are proposing.

Thanks for helping me see a useful side.
 
I've finally gotten a chance to get to the local university library, and use proper databases to investigate antinociceptive agents in the capsaicin pain model. Capsazepine is one in that category among many. More results to come. :)
 
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