Effects of serotonergic compounds on aqueous humor dynamics in monkeys

B'Ann T. Gabelt; J. Cameron Millar; Julie A. Kiland; Jennifer A. Peterson; Jennifer L. Seeman; Paul L. Kaufman

doi:10.1076/ceyr.23.2.120.5477

Effects of serotonergic compounds on aqueous humor dynamics in monkeys

B'Ann T. Gabelt, J. Cameron Millar, Julie A. Kiland, Jennifer A. Peterson, Jennifer L. Seeman, Paul L. Kaufman

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13 Scopus citations

Abstract

Purpose. The effects of several serotonergic agonists on aqueous humor formation (AHF), total outflow facility (OF) and intraocular pressure (IOP) were investigated in living cynomolgus monkeys. Methods. We determined the effect of a single topical unilateral 300 μg or 3 mg dose of the 5-HT agonists serotonin, 5-carboxamidotryptamine (5-CT), sumatripan, gepirone, and 8-hydroxy-2(di-n-propylaminotetralin) (8-OH-DPAT) and a 450 μg dose of flesinoxan on IOP (Goldmann applanation tonometry), AHF (scanning ocular fluorophotometry) and total OF (8-OH-DPAT only, topically and intracamerally). Results. Serotonin, 5-CT, sumatripan or gepirone had no significant effect on IOP or AHF. 8-OH-DPAT caused an AHF increase of ∼70% over 6 hr in both ipsilateral drug- and contralateral vehicle-treated eyes, but no significant change in IOP compared with baseline measured on a separate occasion in the same animals. 8-OH-DPAT did not increase protein levels or rate of entry of systemically administered fluorescein in the anterior chamber aqueous humor compared to historic controls, and no difference was seen between ipsilateral and contralateral eyes. Flesinoxan had no effect on IOP and produced an insignificant 25% increase in flow in treated eyes compared to baseline. Conclusion. The results for 8-OH-DPAT and possibly flexinoxan indicate the presence of a secretion-stimulating 5-HT1A receptor in monkey ciliary epithelium that has little effect on IOP. OF was unchanged following 8-OH-DPAT administered topically or following intracameral exchange.

Original language	English
Pages (from-to)	120-127
Number of pages	8
Journal	Current Eye Research
Volume	23
Issue number	2
DOIs	https://doi.org/10.1076/ceyr.23.2.120.5477
State	Published - 2001

Keywords

8-OH-DPAT
Aqueous humor flow
Intraocular pressure
Outflow facility
Serotonin

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10.1076/ceyr.23.2.120.5477

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@article{e572d7aef459414c8fcf0c676d5e5b0e,

title = "Effects of serotonergic compounds on aqueous humor dynamics in monkeys",

abstract = "Purpose. The effects of several serotonergic agonists on aqueous humor formation (AHF), total outflow facility (OF) and intraocular pressure (IOP) were investigated in living cynomolgus monkeys. Methods. We determined the effect of a single topical unilateral 300 μg or 3 mg dose of the 5-HT agonists serotonin, 5-carboxamidotryptamine (5-CT), sumatripan, gepirone, and 8-hydroxy-2(di-n-propylaminotetralin) (8-OH-DPAT) and a 450 μg dose of flesinoxan on IOP (Goldmann applanation tonometry), AHF (scanning ocular fluorophotometry) and total OF (8-OH-DPAT only, topically and intracamerally). Results. Serotonin, 5-CT, sumatripan or gepirone had no significant effect on IOP or AHF. 8-OH-DPAT caused an AHF increase of ∼70% over 6 hr in both ipsilateral drug- and contralateral vehicle-treated eyes, but no significant change in IOP compared with baseline measured on a separate occasion in the same animals. 8-OH-DPAT did not increase protein levels or rate of entry of systemically administered fluorescein in the anterior chamber aqueous humor compared to historic controls, and no difference was seen between ipsilateral and contralateral eyes. Flesinoxan had no effect on IOP and produced an insignificant 25% increase in flow in treated eyes compared to baseline. Conclusion. The results for 8-OH-DPAT and possibly flexinoxan indicate the presence of a secretion-stimulating 5-HT1A receptor in monkey ciliary epithelium that has little effect on IOP. OF was unchanged following 8-OH-DPAT administered topically or following intracameral exchange.",

keywords = "8-OH-DPAT, Aqueous humor flow, Intraocular pressure, Outflow facility, Serotonin",

author = "Gabelt, {B'Ann T.} and Millar, {J. Cameron} and Kiland, {Julie A.} and Peterson, {Jennifer A.} and Seeman, {Jennifer L.} and Kaufman, {Paul L.}",

note = "Funding Information: This work was supported by grants from the National Eye Institute (EY02698), Bethesda, MD; Research to Prevent Blindness, New York (Senior Scientific Investigator Award to PLK), and the Ocular Physiology Research and Education Foundation (Madison, WI). The authors have no proprietary interests in any of the compounds described. We wish to thank Dr. Neville N. Osborne (Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford OX2 6AW U.K.) for his thoughtful comments, criticisms and suggestions on these studies and this manuscript.",

year = "2001",

doi = "10.1076/ceyr.23.2.120.5477",

language = "English",

volume = "23",

pages = "120--127",

journal = "Current Eye Research",

issn = "0271-3683",

publisher = "Taylor and Francis Ltd.",

number = "2",

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TY - JOUR

T1 - Effects of serotonergic compounds on aqueous humor dynamics in monkeys

AU - Gabelt, B'Ann T.

AU - Millar, J. Cameron

AU - Kiland, Julie A.

AU - Peterson, Jennifer A.

AU - Seeman, Jennifer L.

AU - Kaufman, Paul L.

N1 - Funding Information: This work was supported by grants from the National Eye Institute (EY02698), Bethesda, MD; Research to Prevent Blindness, New York (Senior Scientific Investigator Award to PLK), and the Ocular Physiology Research and Education Foundation (Madison, WI). The authors have no proprietary interests in any of the compounds described. We wish to thank Dr. Neville N. Osborne (Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford OX2 6AW U.K.) for his thoughtful comments, criticisms and suggestions on these studies and this manuscript.

PY - 2001

Y1 - 2001

N2 - Purpose. The effects of several serotonergic agonists on aqueous humor formation (AHF), total outflow facility (OF) and intraocular pressure (IOP) were investigated in living cynomolgus monkeys. Methods. We determined the effect of a single topical unilateral 300 μg or 3 mg dose of the 5-HT agonists serotonin, 5-carboxamidotryptamine (5-CT), sumatripan, gepirone, and 8-hydroxy-2(di-n-propylaminotetralin) (8-OH-DPAT) and a 450 μg dose of flesinoxan on IOP (Goldmann applanation tonometry), AHF (scanning ocular fluorophotometry) and total OF (8-OH-DPAT only, topically and intracamerally). Results. Serotonin, 5-CT, sumatripan or gepirone had no significant effect on IOP or AHF. 8-OH-DPAT caused an AHF increase of ∼70% over 6 hr in both ipsilateral drug- and contralateral vehicle-treated eyes, but no significant change in IOP compared with baseline measured on a separate occasion in the same animals. 8-OH-DPAT did not increase protein levels or rate of entry of systemically administered fluorescein in the anterior chamber aqueous humor compared to historic controls, and no difference was seen between ipsilateral and contralateral eyes. Flesinoxan had no effect on IOP and produced an insignificant 25% increase in flow in treated eyes compared to baseline. Conclusion. The results for 8-OH-DPAT and possibly flexinoxan indicate the presence of a secretion-stimulating 5-HT1A receptor in monkey ciliary epithelium that has little effect on IOP. OF was unchanged following 8-OH-DPAT administered topically or following intracameral exchange.

AB - Purpose. The effects of several serotonergic agonists on aqueous humor formation (AHF), total outflow facility (OF) and intraocular pressure (IOP) were investigated in living cynomolgus monkeys. Methods. We determined the effect of a single topical unilateral 300 μg or 3 mg dose of the 5-HT agonists serotonin, 5-carboxamidotryptamine (5-CT), sumatripan, gepirone, and 8-hydroxy-2(di-n-propylaminotetralin) (8-OH-DPAT) and a 450 μg dose of flesinoxan on IOP (Goldmann applanation tonometry), AHF (scanning ocular fluorophotometry) and total OF (8-OH-DPAT only, topically and intracamerally). Results. Serotonin, 5-CT, sumatripan or gepirone had no significant effect on IOP or AHF. 8-OH-DPAT caused an AHF increase of ∼70% over 6 hr in both ipsilateral drug- and contralateral vehicle-treated eyes, but no significant change in IOP compared with baseline measured on a separate occasion in the same animals. 8-OH-DPAT did not increase protein levels or rate of entry of systemically administered fluorescein in the anterior chamber aqueous humor compared to historic controls, and no difference was seen between ipsilateral and contralateral eyes. Flesinoxan had no effect on IOP and produced an insignificant 25% increase in flow in treated eyes compared to baseline. Conclusion. The results for 8-OH-DPAT and possibly flexinoxan indicate the presence of a secretion-stimulating 5-HT1A receptor in monkey ciliary epithelium that has little effect on IOP. OF was unchanged following 8-OH-DPAT administered topically or following intracameral exchange.

KW - 8-OH-DPAT

KW - Aqueous humor flow

KW - Intraocular pressure

KW - Outflow facility

KW - Serotonin

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U2 - 10.1076/ceyr.23.2.120.5477

DO - 10.1076/ceyr.23.2.120.5477

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SN - 0271-3683

VL - 23

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JO - Current Eye Research

JF - Current Eye Research

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ER -

Effects of serotonergic compounds on aqueous humor dynamics in monkeys

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Keywords

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