The foundations of Florey's fame: Howard Florey: The making of a great scientist by G. MacFarlane, Oxford University Press, Oxford, 1979. £6.95 (xii + 392 pages) ISBN 019 858161 0

Abstract

Scientists have been in search of Hippocrates' natural cause of epilepsy, the sacred disease, for centuries. Experimental work in the neurophysiology of epilepsy was initiated late in the nineteenth and early in the twentieth century. The suggestion that inhibitory mechanisms play a major role in the pathogenesis of seizures was put forth by Adrian in 1936. In 1954, Florey provided the first evidence for a neurochemical mechanism for this inhibition with the demonstration of an inhibitory (I) factor in brain extract that proved to be inhibitory to crayfish stretch receptors. Florey's I factor was subsequently identified as γ-aminobutyric acid (GABA)—a compound now generally acknowledged to be a major inhibitory neurotransmitter in the brain. Since the classic paper of Symonds on excitation and inhibition in epilepsy, the various research strategies in this group of diseases have focused more and more on basic excitatory and inhibitory mechanisms in seizures on a cellular as well as a whole-brain level. To understand the complex neurochemistry of seizure states, it is first necessary to define precisely the meaning of the terms “seizure” and “epilepsy” and review the neurophysiology of these aberrant neuronal systems. This chapter discusses various animal models of seizures and reviews the neurochemistry of epilepsy in the context of neurotransmitters and neuroactive agents in animal models, anticonvulsant drug interaction, and the clinical seizure state.