Assessment of the intraocular pressure-lowering activity of bicyclic derivatives of 1-substituted benzyloctahydroisoquinoline

S. L. Saha, I. N. Igbo, Catherine A. Opere, G. L. Zhan, J. Tanimaya, S. E. Ohia, Victoria F. Roche

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In our study of IOP-lowering agents, we have synthesized several bicyclic analogs of 1-benzyloctahydroisoquinoline. The target molecules were synthesized in an eleven-step process. Structures were proved through spectrometry, elemental analysis and, in selected cases, high resolution mass spectrometry. The final products were secondary or tertiary amines containing a 1-benzyl moiety substituted at the p-position with a methoxy, methyl or chloro group. All target molecules were analyzed in 1% solution in distilled water in normotensive rabbits. After topical administration, IOP was monitored in both eyes for up to seven hours. The 1-p-methoxybenzyl molecule 2 was the most active, and caused a maximal IOP drop of 8.8 ± 1.9 (n = 7) mm Hg in the ipsilateral eye at 4 hours post-administration, with only partial recovery at seven hours. All other compounds tested either showed very weak activity (3-6) or were inactive (1). All compounds produced a contralateral effect, and 5 induced rebound ocular hypertension. We conclude that selected tertiary bicyclic 1-p-methoxybenzyl-octahydroisoquinolines, particularly N-methylated structures, exhibit a significant IOP-lowering effect in normotensive rabbits.

Original languageEnglish
Pages (from-to)413-420
Number of pages8
JournalJournal of Ocular Pharmacology and Therapeutics
Volume17
Issue number5
StatePublished - 2001

Fingerprint

Intraocular Pressure
Rabbits
Topical Administration
Ocular Hypertension
Amines
Mass Spectrometry
Spectrum Analysis
Water

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Ophthalmology
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Assessment of the intraocular pressure-lowering activity of bicyclic derivatives of 1-substituted benzyloctahydroisoquinoline. / Saha, S. L.; Igbo, I. N.; Opere, Catherine A.; Zhan, G. L.; Tanimaya, J.; Ohia, S. E.; Roche, Victoria F.

In: Journal of Ocular Pharmacology and Therapeutics, Vol. 17, No. 5, 2001, p. 413-420.

Research output: Contribution to journalArticle

@article{67f45c4f1e4f4029a95a837292ad1ca6,
title = "Assessment of the intraocular pressure-lowering activity of bicyclic derivatives of 1-substituted benzyloctahydroisoquinoline",
abstract = "In our study of IOP-lowering agents, we have synthesized several bicyclic analogs of 1-benzyloctahydroisoquinoline. The target molecules were synthesized in an eleven-step process. Structures were proved through spectrometry, elemental analysis and, in selected cases, high resolution mass spectrometry. The final products were secondary or tertiary amines containing a 1-benzyl moiety substituted at the p-position with a methoxy, methyl or chloro group. All target molecules were analyzed in 1{\%} solution in distilled water in normotensive rabbits. After topical administration, IOP was monitored in both eyes for up to seven hours. The 1-p-methoxybenzyl molecule 2 was the most active, and caused a maximal IOP drop of 8.8 ± 1.9 (n = 7) mm Hg in the ipsilateral eye at 4 hours post-administration, with only partial recovery at seven hours. All other compounds tested either showed very weak activity (3-6) or were inactive (1). All compounds produced a contralateral effect, and 5 induced rebound ocular hypertension. We conclude that selected tertiary bicyclic 1-p-methoxybenzyl-octahydroisoquinolines, particularly N-methylated structures, exhibit a significant IOP-lowering effect in normotensive rabbits.",
author = "Saha, {S. L.} and Igbo, {I. N.} and Opere, {Catherine A.} and Zhan, {G. L.} and J. Tanimaya and Ohia, {S. E.} and Roche, {Victoria F.}",
year = "2001",
language = "English",
volume = "17",
pages = "413--420",
journal = "Journal of Ocular Pharmacology and Therapeutics",
issn = "1080-7683",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - Assessment of the intraocular pressure-lowering activity of bicyclic derivatives of 1-substituted benzyloctahydroisoquinoline

AU - Saha, S. L.

AU - Igbo, I. N.

AU - Opere, Catherine A.

AU - Zhan, G. L.

AU - Tanimaya, J.

AU - Ohia, S. E.

AU - Roche, Victoria F.

PY - 2001

Y1 - 2001

N2 - In our study of IOP-lowering agents, we have synthesized several bicyclic analogs of 1-benzyloctahydroisoquinoline. The target molecules were synthesized in an eleven-step process. Structures were proved through spectrometry, elemental analysis and, in selected cases, high resolution mass spectrometry. The final products were secondary or tertiary amines containing a 1-benzyl moiety substituted at the p-position with a methoxy, methyl or chloro group. All target molecules were analyzed in 1% solution in distilled water in normotensive rabbits. After topical administration, IOP was monitored in both eyes for up to seven hours. The 1-p-methoxybenzyl molecule 2 was the most active, and caused a maximal IOP drop of 8.8 ± 1.9 (n = 7) mm Hg in the ipsilateral eye at 4 hours post-administration, with only partial recovery at seven hours. All other compounds tested either showed very weak activity (3-6) or were inactive (1). All compounds produced a contralateral effect, and 5 induced rebound ocular hypertension. We conclude that selected tertiary bicyclic 1-p-methoxybenzyl-octahydroisoquinolines, particularly N-methylated structures, exhibit a significant IOP-lowering effect in normotensive rabbits.

AB - In our study of IOP-lowering agents, we have synthesized several bicyclic analogs of 1-benzyloctahydroisoquinoline. The target molecules were synthesized in an eleven-step process. Structures were proved through spectrometry, elemental analysis and, in selected cases, high resolution mass spectrometry. The final products were secondary or tertiary amines containing a 1-benzyl moiety substituted at the p-position with a methoxy, methyl or chloro group. All target molecules were analyzed in 1% solution in distilled water in normotensive rabbits. After topical administration, IOP was monitored in both eyes for up to seven hours. The 1-p-methoxybenzyl molecule 2 was the most active, and caused a maximal IOP drop of 8.8 ± 1.9 (n = 7) mm Hg in the ipsilateral eye at 4 hours post-administration, with only partial recovery at seven hours. All other compounds tested either showed very weak activity (3-6) or were inactive (1). All compounds produced a contralateral effect, and 5 induced rebound ocular hypertension. We conclude that selected tertiary bicyclic 1-p-methoxybenzyl-octahydroisoquinolines, particularly N-methylated structures, exhibit a significant IOP-lowering effect in normotensive rabbits.

UR - http://www.scopus.com/inward/record.url?scp=0035194687&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035194687&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 413

EP - 420

JO - Journal of Ocular Pharmacology and Therapeutics

JF - Journal of Ocular Pharmacology and Therapeutics

SN - 1080-7683

IS - 5

ER -