RT Journal Article
SR Electronic
T1 Gate-dependent blockade of sodium channels by phenothiazine derivatives: structure-activity relationships.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 423
OP 431
VO 42
IS 3
A1 V Bolotina
A1 K R Courtney
A1 B Khodorov
YR 1992
UL http://molpharm.aspetjournals.org/content/42/3/423.abstract
AB Voltage-clamp studies of myelinated nerve fibers that are designed to determine structural criteria regarding selective drug blocking of open and inactive states of the sodium channel are described. A series of phenothiazines were studied. It was shown that two of these drugs (ethmozine and ethacizine, at 5 microM) require open channels for blocking action and the other two (chlorpromazine and chloracizine, at 5 microM) can effectively block inactive channels. A size criterion, which looks at the spanning width at the aromatic end of these molecules, can explain this qualitative difference in drug action. Other important differences in the action of these four drugs are described, including their rates of development of drug block and removal of drug block. Relevant critiques of proposed structure-activity hypotheses are given.