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Polyamine amide toxins as pharmacological tools and pharmaceutical agents

Published online by Cambridge University Press:  05 December 2011

Ian S. Blagbrough  and
Peter N. R. Usherwood
Ian S. Blagbrough
Affiliation:
School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
Peter N. R. Usherwood
Affiliation:
Department of Life Science, School of Biological Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.
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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.

Type
Research Article
Information
Proceedings of the Royal Society of Edinburgh, Section B: Biological Sciences , Volume 99 , Issue 1-2: The Advancement of Drug Discovery , 1992 , pp. 67 - 81
Copyright
Copyright © Royal Society of Edinburgh 1992

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