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

Abstract

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.

Role of 1-Adrenoceptor Subtypes in Pupil Dilation Studied With Gene-Targeted Mice

“…32 In support of this concept, a recent study in rabbits suggested that chronic exposure to the a 1 -AR antagonists tamsulosin and silodosin causes atrophy of the iris dilator muscle due to a drug-melanin interaction in adjacent pigment epithelial cells. 17 In the present study, we found no differences in iris dilator muscle thickness between wild-type mice and any of the mouse genotypes lacking a single a 1 -AR subtype. There are several possible explanations for the differences between our observations in mice and the previous in humans and rabbits.…”

“…13,15,16 Thus, it has been proposed that IFIS may result from a combination of pharmacologic inhibition of iris smooth muscle contraction and long-term smooth muscle atrophy related to drug accumulation in adjacent iris pigment epithelial cells. 17 The goal of the present study was to examine the hypothesis that the a 1A -AR subtype mediates pupil dilation and trophic effects in the mouse iris. Moreover, the contribution of the other two a 1 -AR subtypes to these effects has been tested.…”

Korean patients taking α1-adrenergic receptor antagonists show lower incidence of intraoperative floppy iris syndrome than western patients

“…Given that the iris stroma is composed of dense fibrocollagenous tissue with interspersed vessels, melanocytes, and fibroblasts, it is likely that the dilator muscle contributes significantly to the structural rigidity of the iris in the face of hydrostatic forces occurring within the anterior chamber during phacoemulsification 12. Goseki et al 21 reported that the interaction between α1-ARAs and melanin, in addition to the high affinity of α1-ARAs for α1-adrenergic receptors, is another important mechanism of dilator muscle atrophy (based on experiments in albino and pigmented rabbits).…”

Quantitation ofIn Vitroα-1 Adrenergic Receptor Antagonist Binding Capacity to Biologic Melanin Using Tandem Mass Spectrometry

“…6 Recent studies showed differences in tamsulosin and silodosin binding affinity on albino and pigmented rabbit iris dilator muscle have reported a clear distinction in pK b levels between non-pigmented and pigmented animals. 8 It is notable that receptors between pigmented and non-pigmented species display similar pharmacologic character; therefore, differences in the dissociation constant values cannot be fully explained by receptor affinity. 8 Furthermore, it is unclear how the pharmacodynamic consequences of competitive antagonist action relate to differences in receptor affinity between pigmented and non-pigmented species.…”

“…8 It is notable that receptors between pigmented and non-pigmented species display similar pharmacologic character; therefore, differences in the dissociation constant values cannot be fully explained by receptor affinity. 8 Furthermore, it is unclear how the pharmacodynamic consequences of competitive antagonist action relate to differences in receptor affinity between pigmented and non-pigmented species. Binding affinity to melanin has been shown to be strongly related to cationic charge distribution found in basic molecules including both drugs and protein entities such as alpha-1 acid glycoprotein.…”