Drugs Affecting 5-HT Systems

Abstract

It was in the very early hours of a February morning in 1977 that I first looked down the microscope and saw yellow fluorescence, characteristic of 5-hydroxytryptamine (5-HT) in frozen sections of Octopus brain. After struggling for two years with the capricious fluorescence histochemical technique to locate catecholamines and 5-HT, I finally had a successful result, and the PhD that had seemed a remote possibility for many months finally began to look feasible. Given the enormously important topic of this volume – the discovery and development of drugs affecting 5-HT systems – this small excursion into Octopus neurochemistry might seem irrelevant. However, cephalopod molluscs have played important roles in the history of 5-HT. More than 30000 pairs of posterior salivary glands of Octopus vulgaris were used by Vittorio Erspamer, for the first extraction and identification of enteramine, which was later shown to be identical to serotonin discovered by John Gaddum, and chemically characterized as 5-hydroxytryptamine. Other molluscs have provided some of the most sensitive bioassays for 5-HT, as Gaddum and Paasonen described in 1955, and several participants in this Witness Seminar recollected either using such bioassays or investigating invertebrate pharmacology at the beginning of their careers. Many reflected, however, that invertebrate receptors seemed to be very different from those found in mammals; they had, as David Wallis put it, ‘a parallel pharmacology’. One Witness, Merton Sandler, remembered attending a lecture by Vittorio Erspamer in London in the early 1950s, and being intrigued enough to start work on the degradative enzyme monoamine oxidase, a field which became highly significant for the development of a whole class of therapeutic drugs: the monoamine oxidase inhibitors