Abstract
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.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
