About Professor Trevor W Stone

Professor Trevor W Stone

B.Pharm., Ph.D., D.Sc., F.B.Ph.S., Hon. F.R.C.P.

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, work developed during sabbatical periods (1974 and 1977) in Dr. Floyd Bloom’s laboratory at the National Institute for Mental Health in St. Elizabeth’s hospital, Washington DC. During this period he established the technique of microiontophoresis in Aberdeen, a method for applying potential neurotransmitters and drugs to single cortical neurons identified physiologically as pyramidal tract neurons or as neurons responding to afferent, thalamic stimulation. The technique was the subject of a specialized monograph on the origins, theory, applications and future potential of the technique [1].

ORC ID ID is:- 0000-0002-5532-0031

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 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 compounds synthesised by Dr. Jim Collins led to 2-amino-5-phosphonopentanoic acid (2-AP5) and 2-amino-7-phosphonoheptanoic acid (2-AP7) as potent and selective antagonists at N-methyl-D-aspartate (NMDA) receptors [3].

In 1981, these antagonists were used to show that from a series of compounds designed by Prof. Stone one of them – a rigid analogue of glutamate – was a selective agonist at NMDA receptors [4]. This compound was quinolinic acid, a product of the kynurenine pathway of tryptophan oxidation. These findings initiated interest in the excitatory and neurodegenerative properties of quinolinate. 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 [5,6].

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 development could affect 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.

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 he is Honorary Senior Research Fellow at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Disorders (NDORMS), where his current interests are in the integration of neuropharmacological and immunological studies of the kynurenine pathway and their interface in neuroimmune communication.

Honours

He has been awarded a D.Sc. degree of the University of London (1983), he is a Fellow of the British Pharmacological Society (2005) and was made an Honorary Fellow of the Royal College of Physicians in London (2011).

In 2018 he was awarded the Luigi Musajo Medal from the International Society for the Study of Tryptophan and the University of Padua (Italy) for his work on tryptophan metabolism in the kynurenine pathway.

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] Perkins MN, Stone TW (1985) Actions of kynurenic acid and quinolinic acid in the rat hippocampus in vivo. Exp. Neurol. 88, 570-579.