title: Nifedipine enhances the relaxant effects of cyclo-oxygenase inhibitors on the bovine ciliary muscle.
abstract: OBJECTIVE
  The inhibition of cyclo-oxygenase (COX) enzymes and the blockade of Ca (2+) channels play an important role in the regulation of smooth muscle relaxation. This study was designed to investigate the relaxant effects of celecoxib, DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), and indomethacin, cyclo-oxygenase (COX-1 and -2) inhibitors, in the absence or presence of a nifedipine, L-type Ca(2+) channel blocker, on bovine ciliary muscle.
  
  
  METHODS
  Ciliary muscle strips (n = 12) were mounted in organ baths and tested for changes in isometric tension in response to celecoxib, DFU, and indomethacin. The relaxant effects of celecoxib, DFU, and indomethacin on carbachol-induced contractions in the presence or absence of nifedipine were investigated.
  
  
  RESULTS
  Celecoxib (10(-7)-10(-4) M), DFU (10(-7)-10(-4) M), indomethacin (10(-7)-10(-4) M), and nifedipine (10(-7)-10(-4) M) inhibited the carbachol-induced contractions in a concentration-dependent manner. The E(max) value of indomethacin was significantly higher than the E(max) values of celecoxib and DFU in ciliary muscle (P < 0.05), with no significant change in pD(2) values (P > 0.05). The relaxation responses by celecoxib, DFU, and indomethacin were significantly increased in the presence of nifedipine (10(-6) M). There were no significant differences between pEC50 and values of celecoxib, DFU, and indomethacin in the absence of nifedipine (10(-6) M) (P > 0.05), but E(max)values were significantly increased (P < 0.05).
  
  
  CONCLUSIONS
  These results suggest that the celecoxib, DFU, and indomethacin cause relaxation in ciliary muscle precontracted with carbachol. Blockade of calcium channels with nifedipine in ciliary muscle may increase the relaxant effect of celecoxib, DFU, and indomethacin. The topical or systemic use of celecoxib, DFU, and indomethacin with nifedipine can cause blurred near vision due to ciliary muscle relaxation, and in ocular pain conditions caused by ciliary spasm, the pain can be decreased more easily by combined use of these drugs.
authors.affiliation: Department of Ophthalmology, Cumhuriyet University School of Medicine, Sivas, Turkey. ilkertoker@gmail.com
authors.forename: Mustafa
authors.initials: M
authors.lastname: Toker
authors.forename: Ihsan
authors.initials: I
authors.lastname: Bagcivan
authors.forename: Aysen
authors.initials: A
authors.lastname: Topalkara
authors.forename: Baris
authors.initials: B
authors.lastname: Karadas
authors.forename: Nedim
authors.initials: N
authors.lastname: Durmus
authors.forename: Ahmet
authors.initials: A
authors.lastname: Parlak
authors.forename: Tijen
authors.initials: T
authors.lastname: Kaya
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D000068579:Celecoxib; D002924:Ciliary Body / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D011720:Pyrazoles; D013449:Sulfonamides; D009543:Nifedipine; D000068579:Celecoxib; D007213:Indomethacin