title: The structure and ion channel activity of 6-benzylamino-3-hydroxyhexa-cyclo[6.5.0.0(3,7).0(4,12).0(5,10).0(9,13]tridecane.
abstract: A novel compound, 6-benzylamino-3-hydroxyhexacyclo [6.5.0.0(3, 7).0(4, 12).0(5, 10).0(9, 13)]-tridecane, was synthesized as part of an ongoing study to explore the ion channel activity of polycyclic cage amines. The known polycyclic calcium channel antagonist, 8-benzylamino-8, 11-oxapentacyclo [5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane (NGP 1-01) served as the lead compound and as a positive control for channel activity. The title compound inhibited calcium currents at test concentrations of 10 microM at depolarized membrane potentials (in the potential range where the L-type calcium channel inactivates). At the test concentrations modulating effects were also observed for sodium and the delayed rectifier potassium currents. Due to its activity at both Ca(2+) and Na(+) channels, this compound may offer utility as a cardiovascular and/or neuroprotecting agent.
authors.affiliation: Pharmaceutical Chemistry, Potchefstroom University for Christian Higher Education, Potchefstroom, South Africa.
authors.forename: Sarel F
authors.initials: SF
authors.lastname: Malan
authors.forename: Karin
authors.initials: K
authors.lastname: Dyason
authors.forename: Bianca
authors.initials: B
authors.lastname: Wagenaar
authors.forename: J Jurgens
authors.initials: JJ
authors.lastname: Van Der Walt
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Van Der Schyf
mesh_terms: D000818:Animals; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000502:physiology; D051668:Delayed Rectifier Potassium Channels; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D013058:Mass Spectrometry; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: C476025:6-benzylamino-3-hydroxyhexa-cyclo(6.5.0.0(3,7).0(4,12).0(5,10).0(9,13) )tridecane; D001952:Bridged-Ring Compounds; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D026941:Sodium Channel Blockers; D015222:Sodium Channels