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I suspect that keepatg caffeate outside the blood-
braate barrier would also prevent it from enteratg
cells, and therefore havatg any effect
whatsoeveratall. |
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It might allow common sense to migrate across the brain-
keyboard barrier. |
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//But it's unlikely.// Atdeed. |
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A man of your means should be able to afford a keyboard with a working space bar... |
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actually the fluorinated polyglycine was just one version. anything over about 400 AMU does not pass the BBB, yet many proteins are physiologically active so a caffeinated protein that does not pass the BBB might be functional |
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// the thing is that putting a polyglycine on caffeine
would keep it on the non neural side of the blood brain
barrier// |
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And the non-inside side of cell membranes. Caffeine is a
very interesting molecule, it is most fantastically cell
permeable, attaching a polyanything to caffeine is like
shackling a puppy to a caravan. Furthermore it will keep
it out of the active site of phosphodiesterase enzymes,
because it sits RIGHT in there, so you'd bugger up all the
interesting cAMP and PKA effects. Even if you managed to
solve the permeability issue and contrive a clever little
linker to allow the caffeine into the active site, then
you'd bugger up its effects on adenosine receptors
because it sits in the opposite orientation in there. Of
course, there are already drugs which independently
inhibit those two, but who knows about the very
interesting isoform-specific effects on the IP3 gated
Calcium channels? There seems to be a role in there for
mitigating the worst effects of pancreatitis. |
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// like shackling a puppy to a caravan // |
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Is that anything like nailing a kitten to a trailer ? We will pay USD $5.00 cash money to watch that. |
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We'll even supply the nails* free-issue. |
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*Not new ones, mind you. Old, blunt, rusty ones, pulled from the rafters of abandoned lunatic asylums, carrying an ineradicable taint of fear and malign evil, MUHWHAHAHAHA ! |
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Oh, and we will also supply the kittens, and the trailer. |
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Have you determined how the electron resistance across the
neural filaments is to be resolved? |
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Caffeine is pretty small. A big charged molecule glommed onto it might get in the way of the magic. |
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I love caffeine and the side effects as they are. We are
friends. Up close and personal coworkers forever. |
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Leave my damn caffeine alone. It's perfect as it is. (Said
while drinking an energy drink). |
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^ Would you like an espresso with your Red Bull, ma'am? |
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[bsOu0155] aha, yet what about screening a library of like 10,000 compounds on tissue culture to see which are permeable. rather than design a molecule, it is also possible to mass screen, something pharmaceutical companies do now. so caffeine linked to 10,000 other molecules, labeled, then see which make it to the cytoplasm of the human tissue culture, then see if mice remain calm yet get slimmer. |
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Probably the toxic ones would make them slimmer, and also calm because of the dying. |
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//what about screening a library of like 10,000
compounds on tissue culture to see which are permeable.
rather than design a molecule,// |
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We could just screen a library of compounds that are
already validated drugs with known pharmacokinetics,
specificity and all that. But it depends what you want to
achieve. If you want to achieve weight loss, caffeine is
pretty poor. Stupid biology works out and compensates
for it in the medium to long term. Short term it works
reasonably as a stimulant to help you use more energy
during exercise. |
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We have compounds that do what caffeine does, broken
down into individual roles. If you want adenosine
receptor inhibition, there are compounds for all of them
and each sub type. If you want cAMP to rise, there are a
bunch of compounds for that. (If you find a specific, cell
permeable IP3 receptor antagonist, I'd be obliged if you
punt a few milligrams my way.) It is the adenosine
receptor antagonism that gives a short term boost in
metabolism. Mainly by upping heart rate and force and
making it work with a higher blood pressure. Now, we
have stuff that does that a lot better. Ephedrine
increases heart rate AND encourages fat cells to start
releasing their content AND it is an appetite suppressant
AND you'll get faster, at, all the things. It's definitely not
a good idea, however, to be sitting about manipulating
spreadsheets with a 160 bpm heart rate. It also doesn't
go a long way to solving the principle problem, a large
stored quantity of fat. In principle with a fast enough
heart rate and long enough you could burn through 10's of
pound of fat, but that's going to leave you needing a new
heart. It is a better idea to get as many cells as possible
in on the whole burning fuel idea. This is easy, a little
thyroxine will flip a nice built-in metabolism switch. Now
metabolites start charging around and the pounds fall
off. This works by increasing the amount of heat
production, which is responsible for around 25% of all the
oxygen we use. The mechanism isn't solved, but
essentially you make the mitochondria a little leaky. Lots
of fuel gets burned pumping ions into leaky bags. The
downside of thyroxine is that it burns everything,
carbohydrate, protein and fat. So you loose muscle. Also,
your body notices the high thyroxine and thinks it messed
up and turns the thyroid off. This leaves 2,4 DNP. This
creates a very specific ion leak, is invisible to the thyroid
and burns fat-derived NADH very well. The
pharmacokinitecs and theraputic range, however are
horrible. It is also mildly explosive. Unfortunately, there's
no free lunch. |
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//It is also mildly explosive. // |
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How explosive, exactly? I ask for a very good
reason. I bought 500g of DNP from Sigma, which
came as a powder moistened with water
(presumably for this very reason). |
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In order to work with it, I need it dry, so I left the
bottle open in an incubator at about 50°C and
monitored the loss in mass until it plateaued,
leaving me with a bottle of very dry DNP, which is
sitting quite peacefully on a shelf. |
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So, should I be expecting this stuff to go bang in a
spontaneous way? |
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//So, should I be expecting this stuff to go bang in a
spontaneous way?// |
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It's more that it has a low flash point. It might be prudent to
aliquot what you need and re-wet the rest. 500g is not
insignificant. Trinitrophenol on the other hand is a lot more
peppy. Popular in WW1, slightly more powerful than TNT. |
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I know I must be wrong, could you just attach
An alkane like a propyl to one of the carbons on the phenol so
it is more stable then adjust alkane length (as well as position
) to optimize DNP, and while I am omitting sensible
preresearch what about triheptyl xanthine instead of
trimethyl xanthine (caffeine). Resized alkanes are well known
it just seems like they might work or feel pleasant |
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//It's more that it has a low flash point.// |
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Ah, well, that's OK then. As long as it's not either
spontaneously pyrophoric or particularly impact
sensitive I'll take my chances. But I may experiment,
pyrotechnically, with a smaller amount just for the
fun of it. |
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<some time later> Well, that was disappointing.
Half a gram of DNP on a spatula in a Bunsen flame
just sort of burns moodily.<\stl> |
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