Polyamine amide toxins as pharmacological tools and pharmaceutical agents

Abstract

Synopsis:The polyamine amides comprise a newly-discovered class of compounds which exhibits considerable potential for the development of selective pharmacological tools and pharmaceutical agents. In mammals and other vertebrates, they are selective, non-competitive antagonists of ionotropic glutamate receptors, but they also interact with other ionotropic receptors (e.g. nicotinic acetylcholine receptors). Thus, they are channel blockers which are selective for cation channels. We report on synthetic studies undertaken to produce hybrid analogues of these toxins based upon the argiotoxins of spider venoms and the philanthotoxins of parasitic, predatory wasp venom. The synthesis and characterisation of a mono-acylated spermine is also described. In addition, an account of current views on the many possible sites and modes of actions of the polyamine amides is presented and their potential for therapeutic neurochemistry, e.g. for the possible treatment of ischaemic damage to the nervous system, is highlighted.