COX-inhibiting nitric oxide donator
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COX-inhibiting nitric oxide donators (CINODs), also known as NO-NSAIDs, are a new class of non-steroidal anti-inflammatory drug (NSAID) developed with the intention of providing greater safety than existing NSAIDs.
These compounds were first described by John Wallace[SUP][/SUP] and colleagues. CINODs are compounds generated by the fusion of an existing NSAID with a nitric oxide (NO)-donating moiety by chemical means, usually by ester linkage. CINODs retain the anti-inflammatory efficacy of NSAIDs via inhibition of cyclooxygenase (COX) while arguably improving upon gastric and vascular safety, most likely via vasorelaxation, inhibition of leukocyte adhesion and inhibition of caspases, all known effects of NO.
The first CINODs were developed in the 1990s, and as yet none have been approved for use by the general public. The importance of developing such drugs was increased when COX-2-specific NSAIDs rofecoxib (Vioxx) and lumiracoxib (Prexige) were removed from major pharmaceutical markets in the mid-2000s due to vascular safety concerns. In addition, traditional NSAIDs increase blood pressure and interfere with the actions of antihypertensive drugs. Several CINODs are currently being tested in clinical trials, the most advanced of which are being conducted by the French pharmaceutical company NicOx, whose flagship compound naproxcinod (NO-naproxen, nitronaproxen) is in phase III trials for the treatment of osteoarthritis.[SUP][/SUP] Naproxcinod is a fusion of naproxen and a NO-donating group. Other CINODs are also being tested by NicOx for the treatment of diseases in which inflammation plays a role.[SUP][/SUP]
Pretty cool but the FDA said no to it.. Cox inhibitor + Nitric oxide!
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We need to reduce Cox-2 in the skin so PGD2 goes back as per normal without reducing Cox-1 by preserving or boosting it.. Cox-1 is needed for the production of PGE1.. by using Minoxidil, Miconazole Nitrate...
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Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?
UND Life Sciences, #205, 2477 Overlook Road, Cleveland Heights, OH 44106, USA.
Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane A2 (TXA2). On the other hand, aspirin blocks both COX-1 and COX-2 enzymes without decreasing PGI2 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease (CHD). The inhibitory action of aspirin on COX-1 and COX-2 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These fatty acids form precursors to PGE1, PGI2, PGI3, lipoxins (LXs), and resolvins that have anti-inflammatory actions. In contrast, increase in the concentrations of DGLA, AA, EPA, and DHA is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. COX-2 inhibitors interfere with the formation of LXs and resolvins that have neuroprotective and cardioprotective actions. EPA and PGI2 have anti-arrhythmic action. EPA, DHA, and AA augment eNO formation that prevents atherosclerosis. This suggests that COX-2 inhibitors increase cardiovascular and stroke risk by interfering with the formation of eNO, PGI2, LXs, and resolvins and implies that combining EFAs with COX-2 inhibitors could prevent these complications.
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Straight from Wikipedia.... Sprecher's shunt chart... yep... western diet is highly inflammatory... too much omega 6!!
I've been reading your posts to articles and I'm confused on a few points you made. Hope you can give me some insight.
You mentioned on page 75 of this thread that:
"Minoxidil, Miconazole Nitrate or Nitroglycerin cream all upregulates PGE1. PGE1 is the major hair growth booster from the prostaglandins family. DGLA is the immediate precursor of PGE1. (Prostaglandin E1). PGE1 counteracts PGE2 as well."
1. Why is counteracting PGE2 good? Isn't there a lot of evidence pointing to block PGD2 and increase PGE2 to combat hairloss? I'm confused about this since minoxidil increases PGE1 but also PGE2, but PGE2 also causes inflammation. My guess is it's not the up regulation of PGE2 from minoxidil that is beneficial for hair at all, in fact it's what makes minoxidil sort of a double edged sword: allows dead hairs to grow back, but in the meantime it's also causing inflammation and causing more hairloss underneath.
2. DGLA or Dihomo-γ-linolenic acid, I think is a pretty rare form of omega 6 fatty acid. "They" say that the omega 3 to omega 6 balance is important and the western diet is too rich in omega 6, but if we are able to get just DGLA, would taking it do you think would cause inflammation? since it is omega-6. I'm trying to figure out how I can increase PGE1 without increasing PGE2.