Effects of bunazosin hydrochloride on ciliary muscle constriction and matrix metalloproteinase activities.
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.
Akaishi
Takahiro
T
Research and Development Center, Santen Pharmaceutical Co, Ltd, Nara, Japan. takahiro.akaishi@santen.co.jp
Takagi
Yasutaka
Y
Matsugi
Takeshi
T
Ishida
Naruhiro
N
Hara
Hideaki
H
Kashiwagi
Kenji
K
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
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