Modifications to the tetracaine scaffold produce cyclic nucleotide-gated channel blockers with widely varying efficacies.
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.
Strassmaier
Timothy
T
Department of Physiology and Pharmacology and Neurological Sciences Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
Uma
Ramalinga
R
Ghatpande
Ambarish S
AS
Bandyopadhyay
Tapasree
T
Schaffer
Michelle
M
Witte
John
J
McDougal
Patrick G
PG
Brown
R Lane
RL
Karpen
Jeffrey W
JW
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
D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D013748:Tetracaine