Use of polyamines as ionic-channel regulating agents

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The disclosure of any and all cited documents including literature and patent application is incorporated by reference in its entirety.
It is understood that in the present specification "ionic channel regulating agents" shall mean compounds and compositions which regulate flow of a cation by acting directly on a channel or by acting indirectly on it (e.
g.
, by acting on another substance or cellular structure which in turn influences the function of an ionic channel).
Further, "block" shall mean the interruption of ion transport, with direct or primary block being directly attributed to the effect of the blocking agent, while indirect (or secondary or dependent) block is a result of, or due to the action of, the direct block.
For example, direct block of a calcium channel may effectively block a potassium channel where potassium transport is dependent upon calcium transport.
In accordance with the present invention, certain nonaromatic polyamines have the ability to block calcium channels including P-type calcium channels (i.
e.
channels that display one or more of the characteristics associated with the P-channels first identified in Purkinje cells and described above).
As used herein, "polyamine" will generally refer to a compound that has (a) a dehydroxylated (or decarboxylated) arginine or lysine moiety (or a guanidine moiety) appended to (b) a straight polyamine chain moiety having two or more nitrogens separated by methylene groups.
Illustrative of polyamines useful as ionic channel regulating agents are the following compounds: ##STR2## Examples of compounds having different channel blocking activity or displaying the same type of effect as spermidine when tested i.
p.
in animals (but with substantially greater potency) include derivatives or analogs of the above-listed compounds having, e.
g.
, a dehydroxylated or decarboxylated lysine moiety.
Illustrative of polyamines useful as such regulating agents are the following compounds: ##STR3## wherein x and y are integers independently selected from 3 or 4 and wherein Z is a carbonyl, CH