Mechanism of the Ocular Hypotensive Action of Ketanserin

Chang, Fang‐Chi; Burke, James A.; Potter, David E.

doi:10.1089/jop.1985.1.137

Cited by 31 publications

(20 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Topical applications of 5-HT 1A agonists have been reported to lower intraocular pressure in rabbits [7,10,26]. Topical application of 5-HT 2A antagonists has been reported to lower intraocular pressure in monkeys [6] and rabbits [19], although the mechanisms of their ocular hypotensive effects remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits

Puras

Santafé

Segarra

et al. 2007

Graefes Arch Clin Exp Ophthalmol

View full text Add to dashboard Cite

Taken together, our data suggest that these compounds decrease both tonographic outflow facility and, to a greater extent, aqueous humor inflow, which explains their final effect in ocular normotensive and in alpha-chymotrypsin-induced ocular hypertensive rabbits. Reductions in aqueous humor inflow observed after topical application of natural ergot alkaloids in alpha-chymotrypsin-induced ocular hypertensive rabbits can only be explained by a marked inhibition of active secretion of aqueous humor, since processes involved in aqueous humor formation may probably be altered after alpha-chymotrypsin injection.

show abstract

Section: Discussionmentioning

confidence: 99%

A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits

Puras

Santafé

Segarra

et al. 2007

Graefes Arch Clin Exp Ophthalmol

View full text Add to dashboard Cite

show abstract

“…However, it should be noted that although 5-HT 1A receptor agonists altered aqueous dynamics in monkeys, they failed to lower IOP [9], and therefore the situation may not be so straightforward. Table 1 ) The finding that mRNAs encoding subtypes of the 5-HT 2 receptor are expressed by the human ciliary body is of immediate interest to ophthalmologists, since the 5-HT 2 receptor antagonist ketanserin lowers IOP in rabbits, cats and monkeys [2] and in normotensive [8] and ocular hypertensive [7,22] patients. The mechanism of action of ketanserin is thought to involve an increased rate of aqueous outflow, which would be consistent with the presence of 5-HT 2 receptors in the ciliary muscle.…”

Section: Discussionmentioning

confidence: 99%

Expression of serotonin receptor mRNAs in human ciliary body: a polymerase chain reaction study

Chidlow

Hiscott

Osborne

2004

Graefe's Arch Clin Exp Ophthalmol

View full text Add to dashboard Cite

show abstract

“…Topical ocular administration of 5-HT 2 receptor antagonists resulted in a decrease in IOP in monkeys (Chang et al, 1985) and humans (Mastropasqua et al, 1997), suggesting utility for such compounds in the treatment of ocular hypertension associated with glaucoma. The 5-HT 2 receptor antagonists ketanserin (Mastropasqua et al, 1997) and sarpogrelate (Takenaka et al, 1995) have been shown to significantly lower IOP in glaucoma patients.…”

mentioning

confidence: 99%

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

May¹,

McLaughlin²,

Sharif³

et al. 2003

J Pharmacol Exp Ther

106

View full text Add to dashboard Cite

Published investigations of serotonin-1A (5-hydroxytryptamine 1A ; 5-HT 1A ) receptor agonists and serotonin-2A (5-hydroxytryptamine 2A ; 5-HT 2A ) receptor antagonists in nonprimate species provide conflicting results with regard to their intraocular pressurelowering efficacy. Thus, their therapeutic utility in the treatment of human glaucoma has been confusing. We evaluated the effect of selected 5-HT 1A agonists and 5-HT 2A receptor antagonists on intraocular pressure in a nonhuman primate model, the conscious cynomolgus monkey with laser-induced ocular hypertension. Neither selective 5-HT 1A agonists [e.g., R-8-hydroxy-2-(di-n-propylamino)tetralin and flesinoxan] nor selective 5-HT 2 receptor antagonists [e.g.,pressure in the primate model following topical ocular administration. However, compounds that function as agonists at both the 5-HT 1A and 5-HT 2 receptors were found to effectively lower intraocular pressure in the model: 5-hydroxy-␣-methyltryptamine, 5-methoxy-␣-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine (bufotenine), and 5-methoxy-N,N-dimethyltryptamine. Furthermore, the selective 5-HT 2 receptor agonist R-(Ϫ)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane lowered intraocular pressure in the primate model, demonstrating a pharmacological response associated with activation of the 5-HT 2 receptor. These observations suggest that compounds that function as efficient agonists at 5-HT 2 receptors should be considered as potential agents for the control of intraocular pressure in the treatment of ocular hypertension and glaucoma in humans.Identification of several of the numerous serotonin receptors in ocular tissues of the anterior segment of the eye, including the iris-ciliary body of rabbit (Chidlow et al., 1998) and human (Martin et al., 1992), suggests that this neurotransmitter may play an important role in the regulation of intraocular pressure (IOP). Serotonin (5-hydroxytryptamine; 5-HT) is also found in the aqueous humor of humans (Veglio et al., 1998) and other mammals (Boerrigter et al., 1992). These observations have generated considerable interest in the role that serotonin might have in aqueous humor dynamics and even whether 5-HT might be involved in the development of ocular hypertension and glaucoma. There have been numerous conflicting reports on the effect of 5-HT and various 5-HT receptor ligands on IOP in the rabbit, dog, and humans. These observed differences in IOP response may be due to species differences, route of administration, or the lack of 5-HT receptor selectivity of the agents evaluated. For example, 5-HT has been shown to lower IOP in rabbits following intravenous injection (Chiang, 1974). However, when injected intracamerally in the rabbit, a rise in IOP was observed (Krootila et al., 1987). Furthermore, topical ocular administration of 5-HT to the rabbit was reported to result in either a decrease (Krootila et al., 1987) or an increase (Meyer-Bothling et al., 1993) in IOP.Article, publication date, and citation information can be found at

show abstract

Mechanism of the Ocular Hypotensive Action of Ketanserin

Cited by 31 publications

References 10 publications

A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits

A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits

Expression of serotonin receptor mRNAs in human ciliary body: a polymerase chain reaction study

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Contact Info

Product

Resources

About

Mechanism of the Ocular Hypotensive Action of Ketanserin

Cited by 31 publications

References 10 publications

A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits

A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits

Expression of serotonin receptor mRNAs in human ciliary body: a polymerase chain reaction study

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT1A and 5-HT2 Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Contact Info

Product

Resources

About

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys