title: Effects of bunazosin hydrochloride on ciliary muscle constriction and matrix metalloproteinase activities.
abstract: OBJECTIVE
  To clarify the mechanism by which bunazosin hydrochloride (BZ), a selective alpha1-adrenoceptor antagonist, increases uveoscleral outflow.
  
  
  METHODS
  The effects of BZ on matrix metalloproteinase (MMP) activities in cultured monkey ciliary muscle cells, and on phenylephrine hydrochloride-induced constriction in bovine ciliary muscles, were examined. Also, the possible additive ocular hypotensive effects of BZ and latanoprost (LP) were evaluated in ocular normotensive monkeys.
  
  
  RESULTS
  Although BZ at 10 to 10 M did not increase MMP-2, -3, and -9 activities in the culture medium of ciliary muscle cells, BZ at 10 to 10 M inhibited phenylephrine hydrochloride-induced constriction in ciliary muscles. The maximal reduction in intraocular pressure of concomitant administration of BZ and LP was greater than that of BZ alone and tended to be greater than that of LP alone.
  
  
  CONCLUSIONS
  These findings, in normotensive monkeys, indicate that the mechanism whereby BZ increases uveoscleral outflow is independent of an effect on MMPs and is partly due to relaxation of the ciliary muscle. This effect is different from that of LP, which might help to explain the finding that topical concomitant administration of BZ and LP increased AUC(0-6h) value (IOP reduction) to 201% and 145% of BZ and LP given alone, respectively.
authors.affiliation: Research and Development Center, Santen Pharmaceutical Co, Ltd, Nara, Japan. takahiro.akaishi@santen.co.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Akaishi
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Takagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsugi
authors.forename: Naruhiro
authors.initials: N
authors.lastname: Ishida
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashiwagi
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001082:Aqueous Humor / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002924:Ciliary Body / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004338:Drug Combinations; D007429:Intraocular Pressure / Q000187:drug effects; D007537:Isometric Contraction / Q000502:physiology*; D000077338:Latanoprost; D008252:Macaca fascicularis; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010656:Phenylephrine / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D014129:Trabecular Meshwork / Q000502:physiology
chemical_list: D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D004338:Drug Combinations; D011461:Prostaglandins F, Synthetic; D011799:Quinazolines; D010656:Phenylephrine; D000077338:Latanoprost; C018176:bunazosin; D020782:Matrix Metalloproteinases