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About Professor Trevor W Stone

Trevor Stone graduated from The School of Pharmacy, London University (now University College London, UCL), specialising in pharmacology (1969). He then pursued research for a PhD in neuropharmacology under Prof. J. Laurence Malcolm at the University of Aberdeen, where he was appointed Lecturer (1970). His early research interests were in purine (adenosine) physiology and pharmacology in the brain and peripheral tissues. During this period he established the technique of microiontophoresis in Aberdeen, a method for applying chemical compounds to individual cells. This technique was used to apply a range of potential neurotransmitters and drugs to single neurons identified physiologically as pyramidal tract neurons, or as neurons responding to afferent, thalamic stimulation, in the cerebral neocortex. The technique was the subject of a specialized monograph on the origins, theory, applications and future potential of the technique

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After moving back to the University of London (St George’s Medical School) as a Senior Lecturer (1977), Reader (1983) and Professor of Neuroscience (1986), his work was concentrated on the nervous system and electrophysiological studies of synaptic transmission. He has used extracellular and intracellular recording techniques in vivo and in vitro, especially using microiontophoresis[1].

Professor Stone was among the first to obtain pharmacological evidence, in vivo, for glutamate as an excitatory neurotransmitter in the mammalian brain, by blocking synaptically-induced excitation by the early glutamate antagonist glutamate diethyl ester [2]

His subsequent studies on glutamate led to a collaboration with synthetic chemist Jim Collins and the discovery that 2-amino-5-phosphonopentanoic acid (2-AP5) and 2-amino-7-phosphonoheptanoic acid (2-AP7) were potent and selective antagonists at N-methyl-D-aspartate (NMDA) receptors [3], those compounds still being widely and routinely used today to characterise the roles of these receptors in brain physiology and pathology.

In 1981, these antagonists were used to show that a rigid analogue of glutamate, quinolinic acid, was a selective agonist at NMDA receptors [4], a finding which initiated interest in the excitatory and neurogenerative properties of quinolinate, a product of the kynurenine pathway of tryptophan oxidation. In 1982, examining compounds related to quinolinic acid, another member of this pathway – kynurenic acid – was found to be an antagonist of glutamate, being most potent blocking the NMDA receptor subtype of the receptor [5]. Since 1985, Professor Stone’s electrophysiological studies have largely been performed using hippocampal slices, while in vivo work has focussed on mechanisms of neurodegeneration and neuroprotection. Both quinolinic acid and kynurenic acid are naturally occurring, endogenous compounds in mammals and many other animal species and they have been implicated in a variety of disorders of the brain such as Huntington’s disease, Alzheimer’s disease, schizophrenia, depression, multiple sclerosis, cerebral malaria, and others.

Most recently his work has concentrated on the role of the kynurenine pathway in brain development, with the implication that infection or inflammation during embryonic development could affect brain development in the offspring, altering the balance between quinolinic acid and kynurenic acid concentrations and possibly explaining the emergence of disorders such as schizophrenia in later life.

Other components of the kynurenine pathway include 3-hydroxyanthranilic acid and anthranilic acid. A collaborative clinical study of patients with osteoporosis revealed that the ratio between these compounds was profoundly affected in the disease, recovering to normal values after drug treatment [6]. This suggests that these compounds may be important in the development of inflammation or in the body’s response to an inflammatory or infective stimulus.

Recent and Current posts.

In 1989, Professor Stone moved to take the Established Chair of Pharmacology in the University of Glasgow, where he remained until his retirement from the post in September 2017. He has now moved to the University of Oxford, England, where is Honorary Senior Research Fellow at the Kennedy Institute, where his current interests are in the integration of neuropharmacological and immunological studies of the kynurenine pathway.

He has been awarded a D.Sc. degree of the University of London, he is a Fellow of the British Pharmacological Society and was made an Honorary Fellow of the Royal College of Physicians in London.

Metrics

At 1 January 2018, Professor Stone had published 420 full research papers in conventional, refereed journals, and 13 books. Professor Stone’s ORC ID ID is:- 0000-0002-5532-0031  with an H-factor score of 54 and over 15,000 citations of his work.

References cited above:-

[1]. Stone TW, Microiontophoresis and Pressure Ejection. Wiley & Sons, Chichester

[2] Stone TW. (1976) Blockade by amino acid antagonists of neuronal excitation mediated by the pyramidal tract. J. Physiol (Lond), 257, 187-198.

[3] Perkins MN, Stone TW, Collins JF & Curry K. (1981) Phosphonate analogues of carboxylic acids as amino acid antagonists on rat cortical neurones. Neurosci. Lett. 23, 333-336.                   

[4]  Stone TW & Perkins MN. (1981) Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS. Europ. J.Pharmacol. 72, 411-412.           

[5] Perkins MN, Stone TW (1982) Perkins MN & Stone TW  (1982)  An iontophoretic investigation of the action of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Research 247, 184-187.

[6] Forrest CM, Mackay GM, Oxford L, Stoy N, Stone TW, Darlington LG. (2006) Kynurenine pathway metabolism in patients with osteoporosis after two years of drug treatment.

Clin. Exp. Pharmacol. Physiol.  33, 1078-1087.

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