title: Modifications to the tetracaine scaffold produce cyclic nucleotide-gated channel blockers with widely varying efficacies.
abstract: Five new tetracaine analogues were synthesized and evaluated for potency of blockade of cyclic nucleotide-gated channels relative to a multiply charged tetracaine analogue described previously. Increased positive charge at the tertiary amine end of tetracaine results in higher potency and voltage dependence of block. Modifications that reduce the hydrophobic character at the butyl tail are deleterious to block. The tetracaine analogues described here have apparent affinities for CNGA1 channels that vary over nearly 8 orders of magnitude.
authors.affiliation: Department of Physiology and Pharmacology and Neurological Sciences Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Strassmaier
authors.forename: Ramalinga
authors.initials: R
authors.lastname: Uma
authors.forename: Ambarish S
authors.initials: AS
authors.lastname: Ghatpande
authors.forename: Tapasree
authors.initials: T
authors.lastname: Bandyopadhyay
authors.forename: Michelle
authors.initials: M
authors.lastname: Schaffer
authors.forename: John
authors.initials: J
authors.lastname: Witte
authors.forename: Patrick G
authors.initials: PG
authors.lastname: McDougal
authors.forename: R Lane
authors.initials: RL
authors.lastname: Brown
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Karpen
mesh_terms: D000818:Animals; D002417:Cattle; D054815:Cyclic Nucleotide-Gated Cation Channels; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism; D013329:Structure-Activity Relationship; D013748:Tetracaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D014981:Xenopus
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D013748:Tetracaine