The Acetylcholine Therapy in the Treatment of Schizophrenia - The Experience of Mario Fiamberti in the Hospital of Varese (1937)

In the first half of the 20th century, in most European countries, it was thought that cholinesterase and other drugs that counteract acetylcholine should reduce the manifestations of schizophrenia. In 1937, Fiamberti (1894-1970) introduced the transorbital method of lobotomy which established the use of acetylcholine shock treatment for curing the disturbances of schizophrenia. Accepting the idea that the psychic alterations of schizophrenia were caused by a pathological interruption of nerve conduction at a presumably cortical level, Fiamberti thought he could apply this to the clinical field using the properties of acetylcholine, an acetic ester of choline. Here, we examined, in detail, the contribution of Mario Fiamberti to acetylcholine therapy.

Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine.

The mushroom Amanita muscaria (fly agaric) is widely distributed throughout continental Europe and the UK. Its common name suggests that it had been used to kill flies, until superseded by arsenic. The bioactive compounds occurring in the mushroom remained a mystery for long periods of time, but eventually four hallucinogens were isolated from the fungus: muscarine, muscimol, muscazone and ibotenic acid. The shamans of Eastern Siberia used the mushroom as an inebriant and a hallucinogen. In 1912, Henry Dale suggested that muscarine (or a closely related substance) was the transmitter at the parasympathetic nerve endings, where it would produce lacrimation, salivation, sweating, bronchoconstriction and increased intestinal motility. He and Otto Loewi eventually isolated the transmitter and showed that it was not muscarine but acetylcholine. The receptor is now known variously as cholinergic or muscarinic. From this basic knowledge, drugs such as pilocarpine (cholinergic) and ipratropium (anticholinergic) have been shown to be of value in glaucoma and diseases of the lungs, respectively.

[A perspective on acetylcholine].

This special issue is focused on acetylcholine to mark the hundredth year since its discovery by Dr. Henry Hallett Dale. Some readers may be of the opinion that the available literature on acetylcholine is quite vast and, therefore, there is no scope for more interesting findings. However, when we consider the significance of its physiological roles and discuss its involvement in many severe diseases, acetylcholine remains an intriguing molecule worth to be kept in mind.

Acetylcholine--from Vagusstoff to cerebral neurotransmitter.

This paper is concerned with some of the events in physiology that followed Otto Loewi's description of a substance that he named "Vagusstoff"; events that led eventually to the establishment of acetylcholine as a transmitter substance in the nervous system. Much of the work achieving this recognition of acetylcholine as a neurotransmitter took place in the middle third of the twentieth century; a period that witnessed the dislocation of many people as a result of National Socialist policies in Germany, that country's expansionist conquests, and the Second World War. A few of the people who were obliged to emigrate from Europe played prominent roles in these discoveries. This paper describes some of their achievements and, in a way, pays tribute to them.

ATP and acetylcholine, equal brethren.

Acetylcholine was the first neurotransmitter identified and ATP is the hitherto final compound added to the list of small molecule neurotransmitters. Despite the wealth of evidence assigning a signaling role to extracellular ATP and other nucleotides in neural and non-neural tissues, the significance of this signaling pathway was accepted very reluctantly. In view of this, this short commentary contrasts the principal molecular and functional components of the cholinergic signaling pathway with those of ATP and other nucleotides. It highlights pathways of their discovery and analyses tissue distribution, synthesis, uptake, vesicular storage, receptors, release, extracellular hydrolysis as well as pathophysiological significance. There are differences but also striking similarities. Comparable to ACh, ATP is taken up and stored in synaptic vesicles, released in a Ca(2+)-dependent manner, acts on nearby ligand-gated or metabotropic receptors and is hydrolyzed extracellularly. ATP and acetylcholine are also costored and coreleased. In addition, ATP is coreleased from biogenic amine storing nerve terminals as well as from at least subpopulations of glutamatergic and GABAergic terminals. Both ACh and ATP fulfill the criteria postulated for neurotransmitters. More recent evidence reveals that the two messengers are not confined to neural functions, exerting a considerable variety of non-neural functions in non-innervated tissues. While it has long been known that a substantial number of pathologies originate from malfunctions of the cholinergic system there is now ample evidence that numerous pathological conditions have a purinergic component.

Acetylcholine.

This article traces the development of knowledge about the physiology and pharmacology of acetylcholine and its receptors between 1930 and 2005, with emphasis on contributions by members of the British Pharmacological Society, and by other British pharmacologists and physiologists.