advertisement
Abstract #18331 Published in IGR 3-3
Assessment of the intraocular pressure-lowering activity of bicyclic derivatives of 1-substituted benzyloctahydroisoquinoline
Saha SL; Igbo IN; Opere CA; Zhan GL; Taniyama J; Ohia SE; Roche VFJournal of Ocular Pharmacology and Therapeutics 2001; 17: 413-420
In this study of intraocular pressure (IOP)-lowering agents, several bicyclic analogues of 1-benzyloctahydroisoquinoline were synthesized. The target molecules were synthesized in an 11-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) mmHg in the ipsilateral eye at four 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 five induced rebound ocular hypertension. It is concluded that selected tertiary bicyclic 1-p-methoxybenzyl-octahydroisoquinolines, particularly N-methylated structures, exhibit a significant IOP-lowering effect in normotensive rabbits.
Dr S.L. Saha, Department of Pharmaceutical and Administrative Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
