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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Effects of tamsulosin and silodosin on isolated albino and pigmented rabbit iris dilators: possible mechanism of intraoperative floppy-iris syndrome.
Journal of Cataract and Refractive Surgery 2012 September
PURPOSE: To determine the mechanism of intraoperative floppy-iris syndrome (IFIS) by examining the binding affinity of tamsulosin and silodosin to α-receptors and melanin pigment using control and α(2)-blocker chronically administered in rabbit models.
SETTING: Department of Ophthalmology, Kitasato University School of Medicine, Kanagawa, Japan.
DESIGN: Experimental study.
METHODS: The study was performed in isolated albino and pigmented rabbit iris dilators using pharmacologic and morphologic examinations.
RESULTS: For pharmacologic examinations, the mean pK(B) values (pK(B) = -log K(B), where -log K(B) is the equilibrium dissociation constant of the antagonist-receptor complex) of tamsulosin in albino and pigmented rabbits were 9.10 and 8.08 and those of silodosin, 10.3 and 8.11, respectively. The pK(B) values of tamsulosin and silodosin in albino rabbits were significantly higher than in pigmented rabbits. In the isolated rabbit iris dilator, the maximum contraction evoked by 10(-3) mol/L phenylephrine gradually decreased by repetitive application in the chronic α-blocker-administered models. For morphologic examinations, the sizes of the pigment granules of pigment epitheliums for the α-blocker-administered models were irregular. The shape of shared nucleus of dilator muscles and pigment epitheliums changed to lobular, and the dilator muscle layer was thinner than in the control.
CONCLUSIONS: The high affinity of α-blockers for α(1)-adrenoreceptors is important in the analysis of the mechanism of IFIS. However, IFIS should not be attributed to long-term binding with receptors alone; the drug-melanin interaction causing dilator muscle atrophy is probably the other important factor in the mechanism of IFIS.
SETTING: Department of Ophthalmology, Kitasato University School of Medicine, Kanagawa, Japan.
DESIGN: Experimental study.
METHODS: The study was performed in isolated albino and pigmented rabbit iris dilators using pharmacologic and morphologic examinations.
RESULTS: For pharmacologic examinations, the mean pK(B) values (pK(B) = -log K(B), where -log K(B) is the equilibrium dissociation constant of the antagonist-receptor complex) of tamsulosin in albino and pigmented rabbits were 9.10 and 8.08 and those of silodosin, 10.3 and 8.11, respectively. The pK(B) values of tamsulosin and silodosin in albino rabbits were significantly higher than in pigmented rabbits. In the isolated rabbit iris dilator, the maximum contraction evoked by 10(-3) mol/L phenylephrine gradually decreased by repetitive application in the chronic α-blocker-administered models. For morphologic examinations, the sizes of the pigment granules of pigment epitheliums for the α-blocker-administered models were irregular. The shape of shared nucleus of dilator muscles and pigment epitheliums changed to lobular, and the dilator muscle layer was thinner than in the control.
CONCLUSIONS: The high affinity of α-blockers for α(1)-adrenoreceptors is important in the analysis of the mechanism of IFIS. However, IFIS should not be attributed to long-term binding with receptors alone; the drug-melanin interaction causing dilator muscle atrophy is probably the other important factor in the mechanism of IFIS.
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