title: Methyl and isopropyl N-methylanthranilates attenuate diclofenac- and ethanol-induced gastric lesions in rats.
abstract: OBJECTIVE
  Two natural alkaloids, methyl (M) and isopropyl (I) N-methylanthranilates, with recently demonstrated significant pharmacological activities, were assayed for their possible overall effect on intact gastric mucosa and their protective properties towards the onset of gastric lesions induced by diclofenac (a non-steroidal anti-inflammatory drug, NSAID) or ethanol.
  
  
  METHODS
  The influence of I and M on gastric mucosa integrity was assessed by oral administration in doses of 200mg/kg. The gastroprotective action of I and M in doses of 50, 100 and 200mg/kg was analyzed in the diclofenac and ethanol-induced gastric lesion models in rats. After the treatment, the stomachs of the animals were analyzed (captured by a digital camera). Ulcer scoring, morphometric and histopathological analyses of the stomachs were done.
  
  
  RESULTS
  The oral application of these compounds on their own, even in quite high doses (200mg/kg) did not induce gastric lesions. Both alkaloids exerted a very strong antiulcer activity, even in low doses (50mg/kg), by decreasing the number of lesions caused by the application of either diclofenac or ethanol, eliminating them completely or reducing them to a form of mucosal hyperemia.
  
  
  CONCLUSIONS
  Their possible mechanism of action was discussed and due to their many positive properties including anxiolytic, antidepressant, antinociceptive, anti-inflammatory and gastroprotective activities, as well as a cheap and simple synthetic route for their preparation, methyl and isopropyl N-methylanthranilates, both alike, might represent a cost effective alternative sought for in the treatment of peptic ulcers and/or new safer NSAIDs for pain management.
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia. Electronic address: nikoradulovic@yahoo.com.
authors.forename: Niko S
authors.initials: NS
authors.lastname: Radulović
authors.forename: Ivan
authors.initials: I
authors.lastname: Jovanović
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Ilić
authors.forename: Pavle J
authors.initials: PJ
authors.lastname: Randjelović
authors.forename: Nikola M
authors.initials: NM
authors.lastname: Stojanović
authors.forename: Ana B
authors.initials: AB
authors.lastname: Miltojević
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D004008:Diclofenac / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020011:Protective Agents; C568549:isopropyl N-methylanthranilate; D062367:ortho-Aminobenzoates; D004008:Diclofenac; D000431:Ethanol; C412492:methyl N-methylanthranilate
keywords: Antidepressant; Antinociceptive; Anxiolytic; Diclofenac (PubChem CID: 5018304); Ethanol (PubChem CID: 702); Gastroprotective; Isopropyl N-methylanthranilate (PubChem CID: 570886); Methyl N-methylanthranilate (PubChem CID: 6826); Methyl and isopropyl N-methylanthranilates; NSAID; Ranitidine (PubChem CID: 3001055)