N-Hydroxylation of p-acetophenetidide as a factor in nephrotoxicity

Abstract

vious data reported in the literature. [24][25][26][27][28] In this respect, however, further studies are in progress. Experimental SectionIntrinsic viscosities were measured at 30°. Since the yields of all the poly(amide amines) listed were always practically quantitative, elemental analysis determinations were considered to be irrelevant. This polymerization being a polyaddition, in fact, the values obtained for the products could not be expected to be different from that of the monomeric mixtures. That under the conditions used no other reaction but polyaddition takes place between amines and compounds bearing activated double bonds has been previously demonstrated.29 Polymer Gr To a cooled (5°) solution of 1.94 g of 1,4-bisacryloyl-piperazine30 in 10 ml of ethanol, 9 ml of aqueous 1M ethanolamine and 1 ml of ethanolic 1 M «-dodecylamine were added under nitrogen. The mixture was thoroughly shaken and then kept in the dark at room temperature under a nitrogen atmosphere for 4 days. The solvents were then evaporated under reduced pressure and the product was dried at 45°under vacuum (0.1 mm). The yield was practically quan-

Does Paracetamol Cause Urothelial Cancer or Renal Papillary Necrosis?

“…Although phenacetin is metabolized predominantly to paracetamol, a proportion is converted by cytochrome P-450 to N-hydroxyphenacetin, which in turn is capable of forming both cytotoxic [13,14] and carcinogenic [15][16][17][18][19] derivatives. One of these, ^phenetidine, is cap able of being activated by prostaglandin hydroperoxi dase in the renal medulla [20].…”

In-source formation of N-acetyl-p-benzoquinone imine (NAPQI), the putatively toxic acetaminophen (paracetamol) metabolite, after derivatization with pentafluorobenzyl bromide and GC–ECNICI-MS analysis

“…It is likely that this process involves loss of the sole H atom of the acetamide group as a hydride to form uncharged NAPQI (i.e., CH 3 CO-N C 6 H 4 O) (see (R6)), the intermediate toxic metabolite of acetaminophen formed by CYP-catalyzed oxidation of acetaminophen [1][2][3][4][5][6][7]. The lower the ion-source temperature was, the more NAPQI was formed.…”

“…NAPQI is regarded the ultimate toxic metabolite of acetaminophen. Interestingly, chemical and electrochemical oxidation of acetaminophen in the laboratory may also lead to NAPQI formation [4][5][6][7][8], and, in the presence of GSH, in situ generated NAPQI may be converted non-enzymatically to its GSH conjugate [8]. Formally, NAPQI may be produced from acetaminophen by subtracting each of one H atom from the hydroxylic and the amide groups and release of two electrons (R1).…”

Tramadol Safer and Effective Analgesic to Treat Chronic Pain: A Review

“…Conjugation depletes glutathione, a natural antioxidant. This in combination with direct cellular injury by NAPQI, leads to cell damage and death 31,32 .…”