title: Synthesis, Characterization and Comparison of Local Analgesic, Anti-Inflammatory, Anti-Ulcerogenic Activity of Copper and Zinc Complexes of Indomethacin.
abstract: BACKGROUND
  Non-steroidal anti-inflammatory drugs (NSAID) exert gastrointestinal upset by inhibiting mucosal cyclooxygenase (COX) activity and complexation technique with metals has been adopted to overcome this drawback.
  
  
  OBJECTIVE
  The study aimed to overcome the gastrointestinal side effects associated with indomethacin treatment by synthesizing copper (Cu) and zinc (Zn) complexes of indomethacin along with assessing potential pharmacological effects of these complexes.
  
  
  METHODS
  The characterization of synthesized complexes was done by FT-IR, XRD, UV-Vis, Atomic Absorption Spectroscopy (AAS) and Differential Scanning Calorimetry (DSC). Biological properties as local analgesic activity, anti-inflammatory activity and antiulcerogenic activity were evaluated following radiant heat tail flick, inhibition of rat hind paw edema and inhibition of NSAID induced gastroenteropathy method respectively.
  
  
  RESULTS
  0.3 ml of indomethacin-copper complex demonstrated prominent analgesia at 25 &micro;g/ml dose and 0.3 ml of indomethacin-zinc complex, after 30, 60 and 90 minutes of oral administration, shown significant local analgesia at 25, 50 and 100 µg/ml dose. In antiinflammatory activity assay, indomethacin-copper exhibited significant inhibition at 20 mg/kg dose after 2nd, 3rd and 4th hour of administration whereas indomethacin-zinc illustrated significant inhibition at 10 mg/kg dose after 2nd, 3rd and 4th hour of administration. Anti-ulcerogenic activity study of the complexes exhibited no macroscopic damage to the stomach and intestine, except minor microscopic damage.
  
  
  CONCLUSIONS
  In view of the results, the copper and zinc complexes of indomethacin may be used as better substitutes of the parent indomethacin owing to their minimal side effects with additional pharmacological effects.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka-1000, Bangladesh, and Department of Pharmacy, Northern University Bangladesh, Dhaka-1205. Bangladesh.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Sukul
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka- 1000, Dhaka. Bangladesh.
authors.forename: Saikat Kumar
authors.initials: SK
authors.lastname: Poddar
authors.affiliation: Department of Pharmacy, Northern University Bangladesh, Dhaka- 1205. Bangladesh.
authors.forename: Sanjana
authors.initials: S
authors.lastname: Haque
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka- 1000, Dhaka. Bangladesh.
authors.forename: Sajal Kumar
authors.initials: SK
authors.lastname: Saha
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka- 1000, Dhaka. Bangladesh.
authors.forename: Sreedam Chandra
authors.initials: SC
authors.lastname: Das
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka- 1000, Dhaka. Bangladesh.
authors.forename: Zobaer
authors.initials: Z
authors.lastname: Al Mahmud
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka- 1000, Dhaka. Bangladesh.
authors.forename: S M
authors.initials: SM
authors.lastname: Abdur Rahman
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D002351:Carrageenan; D056831:Coordination Complexes / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D003300:Copper / Q000737:chemistry / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006358:Hot Temperature; D007213:Indomethacin / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy; D010437:Peptic Ulcer / Q000139:chemically induced / Q000473:pathology; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D015032:Zinc / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D056831:Coordination Complexes; D003300:Copper; D002351:Carrageenan; D015032:Zinc; D007213:Indomethacin
keywords: Anti-inflammatory; anti-ulcerogenic activity; differential scanning calorimetry; indomethacin metal complexes; local
  analgesic; spectroscopy