What can toxins tell us for drug discovery?

A.L. Harvey, K.N. Bradley, S.A. Cochran, E.G. Rowan, J.A. Pratt, J.A. Quillfeldt, D.A. Jerusalinsky

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Toxins are of interest in drug design because the toxins provide three-dimensional templates for creating small molecular mimics with interesting pharmacological properties. Toxins are also useful in drug discovery because they can be used as pharmacological tools to uncover potential therapeutic targets. With their high potency and selectivity, toxins are often more useful in functional experiments than standard pharmacological agents. We have used two groups of neurotoxins, the dendrotoxins and the muscarinic toxins (MTs), to explore the involvement of subtypes of potassium ion channels and muscarinic receptors, respectively, in processes involved in cognition and the changes in neuronal properties with aging. From our current work, quantitative autoradiographic studies with radiolabelled dendrotoxins reveal widespread distribution of binding sites throughout rat brain sections, but few differences exist between young adult and aged rats. However, displacement studies with toxin K, which preferentially binds to the Kv1.1 subtype of cloned potassium channel, show the selective loss of such sites in regions of the hippocampus and septohippocampal pathway with aging. MTs have been tested for effects on performance of rats in memory paradigms. MT2, which activates m1 receptors, improves performance of rats in a step-down inhibitory avoidance test, whereas MT3, which blocks m4 receptors, decreases performance when given into the hippocampus. This is the first clear demonstration of a role for m4 muscarinic receptors in cognition.
LanguageEnglish
Pages1635-1640
Number of pages5
JournalToxicon
Volume36
Issue number11
DOIs
Publication statusPublished - Nov 1998

Fingerprint

Drug Discovery
Rats
Potassium Channels
Pharmacology
Cognition
Cholinergic Agents
Hippocampus
Muscarinic M4 Receptors
Aging of materials
Drug Design
Neurotoxins
Muscarinic Receptors
Young Adult
Brain
Demonstrations
Binding Sites
Data storage equipment
Pharmaceutical Preparations
Experiments
dendrotoxin

Keywords

  • drug design
  • toxin analysis
  • dendrotoxin
  • neurotoxin

Cite this

Harvey, A. L., Bradley, K. N., Cochran, S. A., Rowan, E. G., Pratt, J. A., Quillfeldt, J. A., & Jerusalinsky, D. A. (1998). What can toxins tell us for drug discovery? Toxicon, 36(11), 1635-1640. https://doi.org/10.1016/S0041-0101(98)00156-1
Harvey, A.L. ; Bradley, K.N. ; Cochran, S.A. ; Rowan, E.G. ; Pratt, J.A. ; Quillfeldt, J.A. ; Jerusalinsky, D.A. / What can toxins tell us for drug discovery?. In: Toxicon. 1998 ; Vol. 36, No. 11. pp. 1635-1640.
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Harvey, AL, Bradley, KN, Cochran, SA, Rowan, EG, Pratt, JA, Quillfeldt, JA & Jerusalinsky, DA 1998, 'What can toxins tell us for drug discovery?' Toxicon, vol. 36, no. 11, pp. 1635-1640. https://doi.org/10.1016/S0041-0101(98)00156-1

What can toxins tell us for drug discovery? / Harvey, A.L.; Bradley, K.N.; Cochran, S.A.; Rowan, E.G.; Pratt, J.A.; Quillfeldt, J.A.; Jerusalinsky, D.A.

In: Toxicon, Vol. 36, No. 11, 11.1998, p. 1635-1640.

Research output: Contribution to journalArticle

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Harvey AL, Bradley KN, Cochran SA, Rowan EG, Pratt JA, Quillfeldt JA et al. What can toxins tell us for drug discovery? Toxicon. 1998 Nov;36(11):1635-1640. https://doi.org/10.1016/S0041-0101(98)00156-1