Effects of tamsulosin and silodosin on isolated albino and pigmented rabbit iris dilators: possible mechanism of intraoperative floppy-iris syndrome.
OBJECTIVE
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.


METHODS
Department of Ophthalmology, Kitasato University School of Medicine, Kanagawa, Japan.


METHODS
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.
Department of Ophthalmology, Kitasato University School of Medicine, Kanagawa, Japan. gosekikun@aol.com
Toshiaki
T
Goseki
Hitoshi
H
Ishikawa
Shiori
S
Ogasawara
Kimiyo
K
Mashimo
Noriko
N
Nemoto
Yuko
Y
Taguchi
Kazuo
K
Yago
Kimiya
K
Shimizu
D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D007431:Intraoperative Complications; D007498:Iris / Q000187:drug effects* / Q000502:physiology; D007499:Iris Diseases / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008543:Melanins / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D009123:Muscle Hypotonia / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D013577:Syndrome; D000077409:Tamsulosin
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D008543:Melanins; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D010656:Phenylephrine; C095285:silodosin; D000077409:Tamsulosin