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.
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, Nebraska 68178, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Saha
authors.forename: I N
authors.initials: IN
authors.lastname: Igbo
authors.forename: C A
authors.initials: CA
authors.lastname: Opere
authors.forename: G L
authors.initials: GL
authors.lastname: Zhan
authors.forename: J
authors.initials: J
authors.lastname: Taniyama
authors.forename: S E
authors.initials: SE
authors.lastname: Ohia
authors.forename: V F
authors.initials: VF
authors.lastname: Roche
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D005123:Eye / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D011817:Rabbits
chemical_list: D001643:Bridged Bicyclo Compounds; D007546:Isoquinolines