Polyamines and polyamine amides from wasps and spiders.

Introduction One of the aims of our research programme is to determine the molecular architecture of the ion channel buried deep within certain subtypes of glutamic acid-gated receptor (GluR), i.e. ionotropic not metabotropic GluR. This will require an interdisciplinary approach, but selective pharmacological tools are now available with which to begin to classify GluR subtypes. Such tools include polyamine amides, synthetic analogues of certain arthropod toxins. Another aspect of this research is the application of these channel blockers to related signalling systems, e.g. voltage-sensitive Caz+ channels and nicotinic acetylcholine receptors (nAChRs), themselves ligand-gated ion channels (LGICs). Therefore, a practical procedure, to achieve these aims, is the design and development of potent, selective channel blockers, followed by their affinity (radioand/or photo-) labelling for subsequent more detailed studies of the threedimensional array of the ion channels. At the commencement of these studies, polyamine amides were unknown as a class of natural products. We now recognize them as including the most potent, selective non-competitive antagonists of certain LGIC receptors. They are amenable to synthetic manipulation, but their high basicity makes them capricious to work with. Polyamines scavenge carbonic acid from the air, they are preferentially soluble in aqueous rather than organic media, and their preparation often requires a number of protecting and deprotecting steps during the synthetic sequence. Nevertheless, these arthropod venom toxins are potentially powerful tools in basic neuroscience. We have also considered the sites and modes of action of the natural and synthetic polyamine amides and modes of action of the natural and synthetic polyamine amides as a function of their pharmacological selectivity. If the