Ocular Effects of Antimuscarinic Compounds: Is Clinical Effect Determined by Binding Affinity for Muscarinic Receptors or Melanin Pigment?

German, Emma J.; Wood, Diana; Hurst, Mark

doi:10.1089/jop.1999.15.257

Cited by 12 publications

(12 citation statements)

References 14 publications

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“…It remains yet unknown as to why the side effects were more pronounced in our non-Asian cohort with high variation in iris color. Up to now, one can only speculate on the role of ocular melanin and the affinity of atropine for melanin [ 23 ]. This is in line with data from Nishiyama et al, who found no side effects 2 weeks after 0.01% atropine in Japanese children aged between 6 and 12 years [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Side effects of topical atropine 0.05% compared to 0.01% for myopia control in German school children: a pilot study

et al. 2021

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Purpose Based on findings of the Asian low-concentration atropine for myopia progression study, a concentration of 0.05% has been proposed as a good compromise between safety and efficacy for myopia control. However, no data on side effects have been published so far in Caucasian children receiving this dose. Methods Prior to commencement of bilateral atropine treatment with 0.05% atropine, 19 myopic children aged 5 to 15 years were treated in only one eye at bedtime leaving the other eye as a control. Pupil size, accommodation amplitude and near visual acuity were measured at 10:00 a.m. the next day and compared to the untreated contralateral control eye. The results were then compared to a cohort of 18 children whose treatment with 0.01% atropine commenced in a similar fashion. Results Twelve children (63%) reported visual impairment or reading difficulties. Anisocoria was 2.9 ± 1.1 mm. In comparison, 0.01% atropine led to a significantly less anisocoria of 0.8 ± 0.7 mm (p < 0.0001). Accommodation was decreased by − 4.2 ± 3.8 D in 0.05% atropine treated eyes, whereas 0.01% atropine induced hypoaccommodation of − 0.05 ± 2.5 D (p < 0.01). Near visual acuity was not significantly reduced in eyes treated with 0.05% atropine compared to 0.01% atropine (p = 0.26). Conclusion Compared to 0.01%, our data indicate stronger more relevant side effects of 0.05% topical atropine in young Caucasian children with progressive myopia as recently reported in Asian children, potentially compromising acceptance and compliance.

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Section: Discussionmentioning

confidence: 99%

Side effects of topical atropine 0.05% compared to 0.01% for myopia control in German school children: a pilot study

et al. 2021

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“…Non‐saturable binding, as well as internal redistribution of the drug affects the agonist – antagonist interactions and could explain the marked differences between individuals in ocular responses to anti‐muscarinic compounds. From a clinical standpoint, association of the compound with melanin may reduce the concentration of drug available to take effect at the muscarinic receptors (melanin acting as a ‘drug‐reservoir’; German et al ., 1999 ). Aravind Meon et al .…”

Section: Discussionmentioning

confidence: 99%

Pharmacological characterization of muscarinic receptors in dog isolated ciliary and urinary bladder smooth muscle

Choppin¹,

Eglen

2001

British J Pharmacology

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The pharmacological characteristics of muscarinic receptors mediating contraction of dog isolated ciliary muscle were determined and compared to those mediating contraction of dog urinary bladder smooth muscle. (+)‐Cis‐dioxolane induced concentration‐dependent contractions of ciliary muscle (pEC50=7.18±0.07, Emax=453±64 mg, n=19) and urinary bladder isolated smooth muscle (pEC50=6.55±0.07, Emax=11±1 g, n=19). These responses were antagonized by several muscarinic receptor antagonists (pKb values for the ciliary muscle and the bladder smooth muscle, respectively): atropine (8.25±0.14 and 9.21±0.09), pirenzepine (6.31±0.13 and 6.70±0.25), tolterodine (7.97±0.14 and 8.68±0.12), oxybutynin (7.40±0.08 and 7.88±0.12), zamifenacin (6.46±0.19 and 7.69±0.11), S‐secoverine (6.66±0.14 and 8.13±0.07), AQ‐RA 741 (6.16±0.15 and 7.08±0.23), p‐F‐HHSiD (7.10±0.27 and 7.35±0.07) and responses were not antagonized by PD 102807 (up to 100 nM). In urinary bladder smooth muscle, the profile of antagonist pKB values correlated significantly with pKi values at human recombinant m3 muscarinic receptors, suggesting that M3 muscarinic receptors mediated the response. In the ciliary muscle, a significant (P<0.01) correlation was obtained with human recombinant m3 and m5 receptors. Darifenacin displayed insurmountable antagonism at receptors in the bladder. At receptors in the ciliary muscle, it exhibited two phases of antagonism, comprising an initial low affinity (pKB<6) component and a high affinity phase (pKB>8). The role of pigmentation in the atypical behaviour of darifenacin was examined. In blue coloured eyes, darifenacin produced apparent surmountable, competitive antagonism of the responses to (+)‐cis‐dioxolane (pKB=8.76±0.07). The antagonist profile obtained in this tissue suggested the involvement of a site which has the pharmacological attributes of the M5 receptor. We suggest that the dog urinary bladder contracts in response to M3 muscarinic receptor activation. Contraction of the brown‐eyed dog ciliary muscle is more complex and may include involvement of at least two receptors, possibly the M5 and M3 receptor, whereas blue‐eyed dog ciliary muscle may involve a single population of M5 muscarinic receptors. British Journal of Pharmacology (2001) 132, 835–842; doi:

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“…In a study, it has been reported that all of the participants with presbyopia experienced marked improvement in near vision with the unique side effect of short-term dimming in vision due to decreasing of the amount of light which entered into the eye with pupil constriction. 23,24 Recently, it has been reported by Encore Vision/Novartis that EV06 ophthalmic solution including lipoic acid choline ester 1.5% improved binocular near acuity with no loss of the best-corrected distance vision. It is well known that the aging of crystalline lens diminishes the elasticity of the lens through the increasing protein sulfhydryl group oxidation to form protein cross-links, and the lens fibres harden and consequently, this causes accommodative amplitude loss and blurry near vision.…”

Section: • Reduce Inflammationmentioning

confidence: 99%

“…The big advantage is that if it does not work, patients can give up using the drop, as long as no long-term detrimental effects are discovered. 23,24,30 Review Presbyopia FOV Tears, a binocular presbyopia-correcting drop is a combination of parasympathetic, alpha agonists 1 and 2, an anti-cholinesterase and a NSAID. The drop affects the ciliary muscle, which causes a physiological accommodation and a dynamic pseudo-accommodation.…”

Section: • Reduce Inflammationmentioning

confidence: 99%

Update on Presbyopia-correcting Drops

Karanfil¹,

Turgut²

2017

European Ophthalmic Review

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P resbyopia causes diminishing of vision-targeted life quality and occupational performance for most people over 40 years old. It affects the ability to perform visual tasks at near distance such as book reading, handcrafts, stitching, cooking and surgical operation. Although there are some treatment modalities such as surgery, the use of near-glasses and contact lenses for presbyopia, topical drug treatment for pharmacological control of presbyopia is currently a very popular and attractive nonsurgical option. In this review, we tried to summarise the presbyopia drop treatment. KeywordsPresbyopia, para-sympathomimetic, accommodation, ciliary muscle contraction, drop treatment, myosis, lens softening, increased focus depth Disclosure: Feyza Çalis Karanfil and Burak Turgut have nothing to declare in relation to this article. Compliance with Ethics:This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors.Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Presbyopia is progressive age-related reduction in accommodation amplitude and the loss of ability of the eye to focus on near objects. It occurs in almost everyone at around 40 years of age.1-5 Presbyopia affects visual tasks at near distance such as book reading, handcrafts, stitching, cooking and surgical operation. Thus, it causes the diminishing of vision-targeted life quality and occupational performance of many people over 40. [1][2][3][4][5] The physiopathology of presbyopia is not clearly known. However, it has been demonstrated that various factors including the hardening of the lens, changes in the elasticity of the lens capsule, lens dimension, geometry of zonular attachments and ciliary muscle contraction may be responsible for the accommodative loss in presbyopia. 1,2Accommodation in humans is performed by ciliary muscle (CM) and iris sphincter contractions, convergence and changes in the shape and position of the lens. The muscles of the iris and ciliary body are stimulated by the parasympathetic system. The parasympathetic cholinergic stimulation causes the contraction of the CM and myosis, providing the increase of focus depth and the shape and position of the lens both to change and for accommodation to develop. 3In an eye which is un-accommodated and looks at a distant object, CM is relaxed; the anterior zonular fibers (ZF) are stretched by traction from the posterior ZF. Then, anterior ZF flattens the lens. In the accommodated eye, the forward and inward movement of the ciliary muscle allows the tension...

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Ocular Effects of Antimuscarinic Compounds: Is Clinical Effect Determined by Binding Affinity for Muscarinic Receptors or Melanin Pigment?

Cited by 12 publications

References 14 publications

Side effects of topical atropine 0.05% compared to 0.01% for myopia control in German school children: a pilot study

Side effects of topical atropine 0.05% compared to 0.01% for myopia control in German school children: a pilot study

Pharmacological characterization of muscarinic receptors in dog isolated ciliary and urinary bladder smooth muscle

Update on Presbyopia-correcting Drops

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