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weight loss or vitality caffeine that is non CNS

 caffeine, with polyfluoroglyine stays on the body side of the blood brain barrier where it causes slimness(?) and faster reaction times(?)
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Caffeine might actually cause benefits outside of the CNS. I do not actually know, the thing is that putting a polyglycine on caffeine would keep it on the non neural side of the blood brain barrier, removing stimulant effects.

without jitters, people might become slimmer (faster PNS motion, thermogenics) as well as might have faster reaction times. So this is also a non-CNS nootropic!

(exclamation point for caffeine!)

—beanangel, Oct 07 2016

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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.
—MaxwellBuchanan, Oct 08 2016
   

       It might allow common sense to migrate across the brain- keyboard barrier.   

       But it's unlikely.
—8th of 7, Oct 08 2016
   

       //But it's unlikely.// Atdeed.
—MaxwellBuchanan, Oct 08 2016
   

       A man of your means should be able to afford a keyboard with a working space bar...
—Voice, Oct 08 2016
   

       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
—beanangel, Oct 08 2016
   

       // the thing is that putting a polyglycine on caffeine would keep it on the non neural side of the blood brain barrier//   

       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.
—bs0u0155, Oct 08 2016
   

       // like shackling a puppy to a caravan //   

       Is that anything like nailing a kitten to a trailer ? We will pay USD $5.00 cash money to watch that.   

       We'll even supply the nails* free-issue.   

       *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 !   

       Oh, and we will also supply the kittens, and the trailer.
—8th of 7, Oct 08 2016
   

       Have you determined how the electron resistance across the neural filaments is to be resolved?
—whatrock, Oct 08 2016
   

       Caffeine is pretty small. A big charged molecule glommed onto it might get in the way of the magic.
—bungston, Oct 08 2016
   

       I love caffeine and the side effects as they are. We are friends. Up close and personal coworkers forever.   

       Leave my damn caffeine alone. It's perfect as it is. (Said while drinking an energy drink).
—blissmiss, Oct 09 2016
   

       ^ Would you like an espresso with your Red Bull, ma'am?
—whatrock, Oct 09 2016
   

       [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.
—beanangel, Oct 10 2016
   

       Probably the toxic ones would make them slimmer, and also calm because of the dying.
—bungston, Oct 10 2016
   

       //what about screening a library of like 10,000 compounds on tissue culture to see which are permeable. rather than design a molecule,//   

       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.   

       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.
—bs0u0155, Oct 11 2016
   

       //It is also mildly explosive. //   

       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).   

       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.   

       So, should I be expecting this stuff to go bang in a spontaneous way?
—MaxwellBuchanan, Oct 11 2016
   

       //So, should I be expecting this stuff to go bang in a spontaneous way?//   

       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.
—bs0u0155, Oct 11 2016
   

       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
—beanangel, Oct 12 2016
   

       //It's more that it has a low flash point.//   

       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.
—MaxwellBuchanan, Oct 12 2016
   

       <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>
—MaxwellBuchanan, Oct 12 2016
   


 

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