| Dr. Harman 2005-09-24, 12:37 pm |
| [Article in Polish]
Miedzybrodzki R.
Instytut Immunologii i Terapii Doswiadczalnej PAN im. Ludwika
Hirszfelda we Wroclawiu. mbrodzki@iitd.pan.wroc.pl
Since the synthesis of salicylic acid, research into the synthesis of
new nonsteroidal anti-inflammatory drugs (NSAIDs) has continued in two
directions: drugs with higher anti-inflammatory activity and those
causing less adverse side-effects. Several very potent classic,
non-selective NSAIDs were already available in the 1970's, but problems
with their toxicity, especially gastro- and nephrotoxicity, have
remained unsolved. The discovery of two cyclooxygenase (COX) isoforms,
COX-1 and COX-2, was a breakthrough that led to obtaining the so-called
coxibs, which selectively inhibit COX-2. This property makes this kind
of NSAID less gastrotoxic than classic, non-selective NSAIDs. Other
strategies to reduce the toxic effects of NSAIDs were their
applications as prodrugs or purified enantiomers. The latest are the
synthesis of classic NSAIDs combined with a chemical group that serves
as a nitric oxide donor or the synthesis of double
cyclooxygenase/5-lipoxygenase inhibitors.Simple inhibition of
prostaglandin (PG) synthesis cannot completely stop the inflammatory
process. Therefore new agents are tested for their influence on many
other elements of the mechanism of inflammation, e.g. the formation of
inflammatory cytokines, free radicals and biogenic amines by the
stimulated inflammatory cells. Such pleiotropic activity of an NSAID
might increase its
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