Abstract
Nonsteroid anti-inflammatory drugs (NSAIDs) are a structurally diverse group of agents with similar therapeutic effects. They reduce pain, fever and inflammation, and are also associated with lowered risks of cardiovascular disease1 and colon cancer2,3. The biological basis for the therapeutic effects of NSAIDs is their ability to inhibit prostaglandin biosynthesis. The NSAIDs specifically target the bifunctional cyclooxygenase enzyme (COX) which is responsible for the initial rate-limiting conversion of arachidonic acid to prostaglandin G (PGG) and its subsequent conversion to PGH2. This is then converted to other prostanoids4,5.
Keywords
- Multilamellar Vesicle
- Large Unilamellar Vesicle
- Radiotracer Method
- Membrane Network
- Similar Therapeutic Effect
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Willard J, Lange RA and Millis LD. The use of aspirin in ischemic heart diseases. N Engl J Med. 1992; 327: 175–81.
Thun J, Namboodusi MM. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med. 1991; 325: 1593–6.
Rosenberg L, Palmer JR, Zauber AG, Warshauer ME, Stolley PD, Shapiro S. A hypothesis: non-steroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst. 1991; 83: 355–8.
Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB. Arachidonic acid metabolism. Annu Rev Biochem. 1986; 55: 69–102.
Cashman J, McAnulty G. Nonsteroidal anti-inflammatory drugs in postsurgical pain management. Drugs. 1995; 49: 51–70.
Otto JC, DeWitt DL, Smith WL. N-glycosylation of prostaglandin endoperoxide synthases-1 and -2 and their orientations in the endoplasmic reticulum. J Biol Chem. 1993; 268: 18234–42.
Smith WL, Mamert LJ. Prostaglandin endoperoxide synthase: structure and catalysis. Biochem Biophys Acta. 1991; 1083: 1–17.
Masferrer JL, Seibert K, Zweifel B, Needleman P. Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme. Proc Natl Acad Sci USA. 1992; 89: 3917–21.
O’Banion MK, Winn VD, Young DA. cDNA cloning and functional activity of a glucocorticoidregulated inflammatory cyclooxygenase. Proc Natl Acad Sci USA. 1992; 89: 4888–92.
Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM. Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem. 1993; 268: 9049–54.
Maier JAM, Hla T, Maciag T. Cyclooxygenase is an immediate-early gene induced by interleukin1 in human endothelial cells. J Biol Chem. 1990; 265: 10805–8.
Herschman MR. Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer Metastasis Rev. 1994; 13: 241–56.
Picat S, Patrick JL, Garavito RM. The X-ray crystal structure of the membrane protein prostaglandin HZ synthase-1. Nature. 1994; 367: 243–9.
Herbette LG. Membrane pathways for drug/ion channel interactions: molecular basis for pharmacokinetic properties. Drug Dev Res. 1994; 33: 214–24.
Meade EA, Smith WL, DeWitt DL. Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1993; 268: 6610–4.
Mitchell J, Akarasereenont P, Thiemerman C, Flower RJ, Vane JR. Selectivity of nonsteroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci USA. 1994; 90: 11693–7.
Gierse JK, Hauser SD, Creely DP et al. Expression and selective inhibition of the constitutive and inducible forms of human cyclooxygenase. Biochem J. 1995; 305: 479–84.
Masferrer JL, Zweifel BS, Manning PT et al. Selective inhibition of inducible cyclooxygenase-2 in vivo is anti-inflammatory and non-ulcerogenic. Proc Natl Acad Sci USA. 1994; 91: 3228–32.
Copeland RA, Williams JM, Giannaras J et al. Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase. Proc Natl Acad Sci USA. 1994; 91: 11202–6.
Reddy ST, Herschman HK. Ligand-induced prostaglandin synthase requires expression of the TIS 10/PGS-2 prostaglandin synthase gene in murine fibroblasts and macrophages. J Biol Chem. 1994; 269: 15473–80.
Morita I, Schindler M, Regier MK et al. Different intracellular locations for prostaglandin endoperoxide H synthase-1 and -2. J Biol Chem. 1995; 270: 10902–8.
Colvin RA, Ashauaid TF, Herbette LG. Structure function studies of canine cardiac sarcolemmal membranes. Estimation of receptor site densities. Biochim Biophys Acta. 1985; 812: 601–8.
Rhodes DG, Sarmiento JG, Herbette LG. Kinetics of binding of 1,4-dihydropyridine to cardiac sarcolemmal receptors: diffusion limited rates for a membrane bilayer approach to the active site. Mol Pharmacol. 1985; 27: 612–23.
Enoch HG, Strittmatter P. Formation and properties of 100-X-diameter single-bilayer phospholipid vesicles. Proc Natl Acad Sci USA. 1979; 76: 145–9.
Chester DW, Herbette LG, Mason RP, Joslyn AF, Triggle DJ, Koppel DE. Diffusion of dihydropyridine calcium channel antagonists in cardiac sarcolemmal lipid multilayers. Biophys J. 1987; 52: 1021–30.
Heider JG, Boyett RL. The picamole determination of free and total cholesterol in cells in culture. J Lipid Res. 1978;19:514–8
Herbette LG, Van Erve YMH, Rhodes DG. Interaction of 1,4-dihydropyridine calcium channel antagonists with biological membranes: lipid bilayer partitioning could occur before drug binding to receptors. J Mol Cardiol. 1989; 21: 187–201.
Avdeef A. pH-Metric log P. II: Refinement of partition coefficients and ionization constants of multiprotic substances. J Pharm Sci. 1993; 82: 1–8.
Shedlovsky T. The behavior of carboxylic acids in mixed solvents. In: Pesce B, editor. Electrolytes. New York: Pergamon Press; 1962: 146–51.
Yasuda M. Dissociation constants of some carboxylic acids in mixed aqueous solvents. Bull Chem Soc Jpn. 1959; 32: 429–32.
Tsai Ruey-Shivan, Carrupt P, Tayar NE, Giroud Y, Andrack P, Testa B. Physiochemical and structural properties of non-steroidal anti-inflammatory oxicams. Hely Chim Acta. 1993; 76: 842–54.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Kluwer Academic Publishers and William Harvey Press
About this chapter
Cite this chapter
Herbette, L.G., Vecchiarelli, M., Trummlitz, G. (1996). NSAID mechanism of action: the role of intracellular pharmacokinetics. In: Vane, J., Botting, J., Botting, R. (eds) Improved Non-Steroid Anti-Inflammatory Drugs: COX-2 Enzyme Inhibitors. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-9029-2_5
Download citation
DOI: https://doi.org/10.1007/978-94-010-9029-2_5
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-9031-5
Online ISBN: 978-94-010-9029-2
eBook Packages: Springer Book Archive