title: Pharmacological screening of glycine amino acid prodrug of acetaminophen.
abstract: OBJECTIVE
  To develop an amino acid prodrug of acetaminophen with comparable therapeutic profile and less hepatotoxicity than acetaminophen.
  
  
  METHODS
  Acetaminophen prodrug was synthesized by esterification between the carboxyl group of amino acid glycine and hydroxyl group of acetaminophen. Analgesic, antipyretic, ulcer healing, and hepatotoxic activities were performed on Wistar rats in this study.
  
  
  RESULTS
  Prodrug showed a 44% inhibition in writhings as compared to 53.3% of acetaminophen. Acetaminophen also offered highest antipyretic activity. Prodrug showed gastroprotective and hepatoprotective effects as it reduced the gastric lesions by 32.1% (P < 0.01) and significantly prevented the rise in liver enzymes (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and bilirubin). The most notable effect of prodrug was in preventing the depletion of hepatic glutathione (GSH), which is reduced by acetaminophen.
  
  
  CONCLUSIONS
  Prodrug showed hepatoprotective and gastroprotective effects, although the therapeutic efficacy was compromised. Prodrug was successful in preventing a decrease in GSH, thereby exhibiting promising results in the field of prodrug designing to avoid the toxic effects of acetaminophen.
authors: VNS Faculty of Pharmacy, Neelbud, Bhopal, India.
authors: Arun
authors: A
authors: Parashar
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D058633:Antipyretics / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005334:Fever / Q000188:drug therapy; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008111:Liver Function Tests; D008297:Male; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy; D011355:Prodrugs / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017208:Rats, Wistar
chemical_list: D018712:Analgesics, Non-Narcotic; D058633:Antipyretics; D011355:Prodrugs; C000604150:glycine-acetaminophen; D000082:Acetaminophen; D005998:Glycine
keywords: Acetaminophen; amino acid; glycine; hepatotoxicity; prodrug