Block of cyclic nucleotide-gated channels by tetracaine derivatives: role of apolar interactions at two distinct locations.
A series of new tetracaine derivatives was synthesized to explore the effects of hydrophobic character on blockade of cyclic nucleotide-gated (CNG) channels. Increasing the hydrophobicity at either of two positions on the tetracaine scaffold, the tertiary amine or the butyl tail, yields blockers with increased potency. However, shape also plays an important role. While gradual increases in length of the butyl tail lead to increased potency, substitution of the butyl tail with branched alkyl or cyclic groups is deleterious.
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR 97239, USA.
Timothy
T
Strassmaier
Sarah R
SR
Kirk
Tapasree
T
Banerji
Jeffrey W
JW
Karpen
D000818:Animals; D000242:Cyclic AMP / Q000037:antagonists & inhibitors*; D006152:Cyclic GMP / Q000037:antagonists & inhibitors*; D015640:Ion Channel Gating / Q000187:drug effects*; D013748:Tetracaine / Q000008:administration & dosage / Q000494:pharmacology*; D014981:Xenopus
D013748:Tetracaine; D000242:Cyclic AMP; D006152:Cyclic GMP