anti inflamatory medications

Since they are both COX inhibitors, I'm assuming it's their steric rather than their reactive properties that are important -- and sterically they are very similar, especially since that amino group off of the sulfur thingy is likely to be protonated in circulation.

I use Oruidus (sp) now and then

patiodog: How can you tell though? (Re: steric hinderance) It's only a 2-D drawing.

Both estradiol (estrogen compound) and testosterone look similar, but have different effects.

Estradiol


Testosterone


I guess my take on it is that chemically the entire compound looks different, but the telling tale in the end would be what part of the molecule is the reactive site and is that reactive site similar on both molecules. I would imagine they must be if they perform similar functions.

Somewhat akin to the differences between progesterone and a progestin analog (lab made) called medroxyprogesterone. They both are supposed to be the same in terms of active sites. However, the natural stuff is almost always the way to go, in my opinion.

Medroxyprogesterone



Progesterone



And I just noticed that testosterone and progesterone look even more alike than do testosterone and estradiol. Once again though, a male hormone and a female hormone.

As always, I enjoy the discussion with you patiodog.

Well, I'm just going about making wild assumptions, but it's been my impression that the synthetics are nowhere near as subtle in their effects as the naturally occurring substances (esp. the steroids). From what I've been able to find so far, in fact, it appears that Vioxx and Celebrex don't even bind the active site on COX-2 -- they bind a secondary site that forces the enzyme into a relatively inactive conformation. (The absence of this site on COX-1 is what gives it its specificity.)

But I'm looking. (Can't make myself work on what I'm supposed to, can't sleep.)

No stereochemical ambiguity in either of those figures, by the way. If you look, everything carbon is either in an aromatic ring or has two identical groups (?) attached.


****

Mardini and Fitzgerald (Mol Intervent. 2001 Apr;1(1):30-8) report two other synthetic COX-2 inhibitors of similar structure in addition to Vioxx and Celebrex. All bind the same site (a pocket that is blocked by valine in COX-2 and a the bulkier isoleucine in COX-1, at identical positions. One of the other two inhibitors actually has a six-membered ring where these two have 5-membered rings. The inhibitor that is most selective for COX-2 (in vitro, anyway) is etoricoxib (the one with the central 6-membered ring), but it acts at much higher concentrations than the rest of them.

All right, ran across a J. Med. Chem. article (Amgad G. Habeeb, P. N. Praveen Rao, and Edward E. Knaus, J. Med. Chem., 44 (18), 3039 -3042, 2001) on the subject. They replaced the sulfur-containing functional groups (I still can't remember the name of that group) of vioxx and celebrex with azide groups and found comparable activity. More to the point, the figures showed the analogs docking in the binding site, and though different groups create different binding affinities (hence the different dosages required for vioxx and celebrex), the drugs are definitely acting through the same electrostatic interactions. The selectivity for COX-2 is all to do with fitting into this particular pocket but being to big to slip into it on COX-1. For what it's worth, COX-2 appears to be the "older" of the two...

And so, back to work...

impressive you folks are!

The secret is that it's all complete nonsense, like Jabberwocky elaborated a million times and stripped of its meter and joy.

Now there's a behavioral trait I relate to.

You both know more chem than I do now, but I like to see/hear you talk about it.

Anemia?

Were you having a gastric bleed?

They may look similar to you, but of course they're very different both in vivo and in vitro. For instance, structural analysis indicates that while Celebrex is a benzenesulfonamide, Vioxx is not. Thus, if a patient is allergic to the sulfonamides, Vioxx may be a better medication for the control of arthritic pain. :wink:

em, miller's question re anemia et al is interesting, but I trust you have good medical purview, Noddy, or what...

Three or four times a year, I'm diagnosed with serious anemia. I've been scoped fore and aft, but the site of the bleeding has not yet been determined. Best theoretical guess is that somewhere I have a malformation of the capillaries and instead of blood flowing from arteries to veins, it escapes and puddles.

Obviously if this is happening in the brain this is exceedingly dangerous. Thus far, my anemia has been a nuisance, but not life threatening.

Eventually it cures itself. Meanwhile, I take iron tonic and mutter about the implacable unfairness of the Genetic Lottery.

V. good to know, thankee. I was just positing that the mechanism of their inhibitory effect is the same; physiology is beyond me.

Medicinal chemistry is the way to search for clues.

Noddy, if your blood puddled in your brain, we wouldn't be talking with you now. I presume you check your stool regularly to make sure it isn't tarry (black) with blood coming from higher up in the alimentary tract.

Two doctors and I all devote time to checking my intact/leaky digestive tract. Thus far there is no helpful evidence.

Vioxx
Health Alert
vioxx has been pulled from the shelf by the manufacturer.
Health risks named are high risk of Heart Attack & stroke

It's sinister that the FDA permits high profit drugs to go on the market without adequate testing. A three year study by Merck, I believe, has discovered the danger to the heart of Vioxx. This is AFTER years of high profits. But the irony in this is that the FDA resists the release of drugs onto the market that serve fewer people who are in serious danger of dying from terminal illnesses. The FDA acts like a "responsible" gatekeeper for drugs desperately needed by fewer people and prematurelyl releases drugs that more dangerously treat MANY people suffering common and non-life threatening complaints like osteoarthritis. It all seems to be about profits, little else.

i've used vioxx , have a v.good opinion about it .but would like to know if it could bring any help i sciatic case?