The concept of chemical transmission in the nervous system arose in the early years of the century when it was discovered that the functioning of the autonomic nervous system was largely dependent on the secretion of acetylcholine and noradrenaline from the parasympathetic and sympathetic nerves respectively. The physiologist Sherrington proposed that nerve cells communicated with one another, and with any other type of adjacent cell, by liberating the neurotransmitter into the space, or synapse, in the immediate vicinity of the nerve ending. He believed that transmission across the synaptic cleft was unidirectional and, unlike conduction down the nerve fibre, was delayed by some milliseconds because of the time it took the transmitter to diffuse across the synapse and activate a specific neurotransmitter receptor on the cell membrane.

While it was generally assumed that the brain also contained acetylcholine and noradrenaline as transmitters, it was only in the early 1950s that experimental evidence accumulated that there were also many other types of transmitter in the brain. The indoleamine neurotransmitter 5-hydroxytryptamine (5-HT), or serotonin, which is now recognized as an important component of mental function, was first studied by Erspamer in Italy and by Page in the United States in enterochromaffin tissue and platelets, respectively. It was left to Gaddum and colleagues in Edinburgh to show that 5-HT was present in the mammalian brain where it may have neurotransmitter properties. The potential importance of 5-HT to psychopharmacology arose when Woolley and Shaw in the United States suggested that lysergic acid diethylamide (LSD) owed its potent hallucinogenic properties to its ability to interfere in some way with brain 5-HT, the similarity in chemical structure of these molecules suggesting that they might compete for a common receptor site on the neuronal membrane.

Fundamentals of Psychopharmacology. Third Edition. By Brian E. Leonard 2003 John Wiley & Sons, Ltd. ISBN 0 471 52178 7

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