Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Med Chem
2005 Sep 08;4818:5805-12. doi: 10.1021/jm0502485.
Show Gene links
Show Anatomy links
Modifications to the tetracaine scaffold produce cyclic nucleotide-gated channel blockers with widely varying efficacies.
Strassmaier T, Uma R, Ghatpande AS, Bandyopadhyay T, Schaffer M, Witte J, McDougal PG, Brown RL, Karpen JW.
???displayArticle.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.
???displayArticle.pubmedLink???
16134947 ???displayArticle.pmcLink???PMC2467444 ???displayArticle.link???J Med Chem ???displayArticle.grants???[+]
Becchetti,
Cyclic nucleotide-gated channels. Pore topology studied through the accessibility of reporter cysteines.
1999, Pubmed,
Xenbase
Becchetti,
Cyclic nucleotide-gated channels. Pore topology studied through the accessibility of reporter cysteines.
1999,
Pubmed
,
Xenbase Catterall,
Molecular mechanisms of gating and drug block of sodium channels.
2002,
Pubmed Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed Eismann,
A single negative charge within the pore region of a cGMP-gated channel controls rectification, Ca2+ blockage, and ionic selectivity.
1994,
Pubmed
,
Xenbase Fesenko,
Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment.
,
Pubmed Flynn,
Conformational changes in S6 coupled to the opening of cyclic nucleotide-gated channels.
2001,
Pubmed
,
Xenbase Fodor,
Mechanism of tetracaine block of cyclic nucleotide-gated channels.
1997,
Pubmed
,
Xenbase Fodor,
Tetracaine reports a conformational change in the pore of cyclic nucleotide-gated channels.
1997,
Pubmed
,
Xenbase Ghatpande,
A multiply charged tetracaine derivative blocks cyclic nucleotide-gated channels at subnanomolar concentrations.
2003,
Pubmed Haynes,
Block of the cyclic GMP-gated channel of vertebrate rod and cone photoreceptors by l-cis-diltiazem.
1992,
Pubmed Haynes,
Single cyclic GMP-activated channel activity in excised patches of rod outer segment membrane.
,
Pubmed Heginbotham,
A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels.
1992,
Pubmed
,
Xenbase Heinemann,
Calcium channel characteristics conferred on the sodium channel by single mutations.
1992,
Pubmed
,
Xenbase Henn,
Probing the transmembrane topology of cyclic nucleotide-gated ion channels with a gene fusion approach.
1995,
Pubmed Jiang,
X-ray structure of a voltage-dependent K+ channel.
2003,
Pubmed Karpen,
Gating kinetics of the cyclic-GMP-activated channel of retinal rods: flash photolysis and voltage-jump studies.
1988,
Pubmed Kaupp,
Cyclic nucleotide-gated ion channels.
2002,
Pubmed Kramer,
Spanning binding sites on allosteric proteins with polymer-linked ligand dimers.
1998,
Pubmed
,
Xenbase Liu,
Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function.
1996,
Pubmed Lu,
Blockade of a retinal cGMP-gated channel by polyamines.
1999,
Pubmed Nakamura,
A cyclic nucleotide-gated conductance in olfactory receptor cilia.
,
Pubmed Ragsdale,
Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.
1996,
Pubmed Ragsdale,
Molecular determinants of state-dependent block of Na+ channels by local anesthetics.
1994,
Pubmed
,
Xenbase Root,
Identification of an external divalent cation-binding site in the pore of a cGMP-activated channel.
1993,
Pubmed
,
Xenbase Ruiz,
Single cyclic nucleotide-gated channels locked in different ligand-bound states.
1997,
Pubmed
,
Xenbase Sunami,
Sodium channel selectivity filter regulates antiarrhythmic drug binding.
1997,
Pubmed
,
Xenbase Varnum,
Subunit interactions in the activation of cyclic nucleotide-gated ion channels.
1996,
Pubmed Weitz,
Subunit stoichiometry of the CNG channel of rod photoreceptors.
2002,
Pubmed Woodhull,
Ionic blockage of sodium channels in nerve.
1973,
Pubmed Zheng,
Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit.
2002,
Pubmed
,
Xenbase Zhong,
The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry.
2002,
Pubmed Zimmerman,
Hindered diffusion in excised membrane patches from retinal rod outer segments.
1988,
Pubmed Zimmerman,
Cyclic GMP-sensitive conductance of retinal rods consists of aqueous pores.
,
Pubmed
