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Fellows Directory

Arnold Burgen

Sir Arnold Burgen FMedSci FRS

Fellow


Elected: 1964

Biography

Arnold Burgen is a physiologist and pharmacologist whose main work has been with drugs that are involved in the nervous control of biological systems. His particular concern is with the nature of drug-receptor interactions at the acetylcholine receptor, important in the central nervous system and in the control of muscle and secretion. He pioneered the use of molecular kinetics and NMR in pharmacology.

One of his detailed studies concerned the M-type receptor for the neurotransmitter acetylcholine. Despite considerable selectivity of agonist activity, related to drug structure and sites of action at this receptor, antagonists did not show selection. However, pirenzepine, a newly synthesised antagonist , showed diversity of binding by M-type receptors in different tissues. In the central nervous system it revealed the existence of at least three subtypes of the receptor with differences in distribution in various areas of the brain. Later genetic studies by others have shown that there are in fact five subtypes.

Radiolabelled irreversible antagonists enabled the visualisation of receptors at the cellular level in the central nervous system.

Tetraethylammonium provided the first evidence of non-competitive antagonism at this receptor and revealed a second site on the receptor that exerts allosteric modification of the main binding site.

Botulinum toxin, which blocks transmission at the neuromuscular junction but not by action on the post-synaptic receptor was shown to act at a presynaptic site that irreversibly prevented the release of acetylcholine. This toxin has proved to be an important therapeutic.

The use of molecular kinetics and NMR to study fine details of receptor activity showed the presence of fast interconversion of different states of receptors, in for example, the important drug target enzymes, carbonic anhydrase and dihydrofolate reductase including the presence of short lived intermediate states. The population of these states were correlated with the structure of various ligands. The drug interactions involve important electrostatic components. The studies highlight the underlying complexity of drug action at receptors.

He is a Fellow Academy of Medical Science, a Foreign Member US National Academy of Science, a Mitglieder Deutsche Akademie der Naturforscher Leopoldina and Member Academia Europaea. He was also previously the Former Director, National Institute for Medical Research, Mill Hill and the Former Sheild Professor of Pharmacology Cambridge University.

Awards

  • Florey Lecture

    Order and disorder: targets for drug action.

  • UK-Canada Rutherford Lecture

    On 'Conformation and selectivity in receptors'.