Use of polyamines as ionic-channel regulating agents
AssigneeNew York University
InventorsBruce D. Cherksey, Rodolfo R. Llinas, Mutsuyuki Sugimori
Life of this patent
Estimating the term…
Abstract
Methods for regulating cation transport across cellular membranes possessing cation channels are provided. The cell membrane possessing a specific ion channel is exposed to a non-aromatic polyamine compound having a lysine- or arginine-based moiety (or a guanidine moiety) coupled to a straight chain polyamine. These polyamines as well as a method for regulating NMDA through a spermidine-like effect on NMDA receptors by exposing a cell membrane to selected polyamines are also provided.
Claims23
A method for regulating calcium transport across cellular membranes possessing calcium channels comprising exposing a cell membrane possessing said channels to the presence of at least one non-aromatic polyamine compound of the formula:
- ##STR8## wherein x and y are integers independently selected from 3 or 4 and wherein Z is a carbonyl, CH.sub.2, or single bond;
- said polyamine being present in an amount effective to block conductance of said channel without having a substantial direct effect on the conductance of other ions.
A compound of the formula:
- ##STR9## wherein x, y are integers independently selected from 3 or 4 and wherein Z is carbonyl, CH.sub.2, or a single bond.
A compound of the formula:
- R--Z--NH--(CH.sub.2).sub.n --NH.sub.2 (II)
- wherein n is an integer between 6 and 12 inclusive, R is HN.dbd.C(NH.sub.2 --NH--(CH.sub.2).sub.3 --CH(NH.sub.2) and Z is selected from the group consisting of CO, CH.sub.2, or a single bond.
A method for regulating potassium transport across cellular membranes possessing potassium channels comprising exposing a membrane possessing said channels to the presence of at least one compound of the formula:
- R--Z--NH--(CH.sub.2).sub.n --NH.sub.2
- wherein n is an integer between 6 and 12 inclusive, R is HN.dbd.C(NH.sub.2)--NH--(CH.sub.2).sub.3 --CH(NH.sub.2) and Z is selected from the group consisting of CO, CH.sub.2, or a single bond;
- said compound being present in an amount effective to block conductance of said channels.
A compound of the formula:
- R--Z--NH--(CH.sub.2).sub.x --NH--(CH.sub.2).sub.y --NH.sub.2 (III)
- wherein R is [H.sub.2 N--(CH.sub.2).sub.4 --CH(NH.sub.2) or HN.dbd.C(NH.sub.2 D)--NH--(CH.sub.2).sub.5 --CH(NH.sub.2)]HN.dbd.C(NH.sub.2)--NH--(CH.sub.2).sub.3 --CH(NH.sub.2);
- Z is carbonyl, CH.sub.2 or a single bond;
- and x, y are integers independently selected from 3 or 4.
A compound of the formula:
- ##STR10## wherein t is zero or 1;
- l is 3 or 4;
- and
- m is 3 or 4 when t is 1 and m is zero when t is zero.
A method for regulating sodium conductance in cell membranes possessing sodium channels comprising exposing a cell membrane possessing said channels to the presence of a compound of the formula:
- ##STR11## wherein t is zero or 1;
- l is 3 or 4;
- and
- m is 3 or 4 when t is 1 and m is zero when t is zero;
- said compound being present in an amount sufficient to block conductance of said channels.
Dependencies are inferred from the claim text.