Physiology of Botulinus Toxin

Abstract

cated that its action is chiefly on the peripheral rather than the central nervous system.1 It has also been shown that the nerve trunk and muscle probably are not involved in the poisoning.2 By a process of elimination it has therefore been reasoned that poisoning occurs at the myoneural junction. On the basis of pathologic studies, however, effects of botulinus toxin on the central nervous system have been described, but there is little agreement among the various reports.3 Moreover, action of the toxin has been compared to that of curare because the two substances act at approximately the same point in the peripheral nervous system.1b This idea has persisted strongly; but, as will be shown later, it appears to be without foundation.It has been the purpose of the present investigation to obtain additional evidence for localizing the action of botulinus toxin and to investigate the equally important question of the manner in which the toxin produces its effects. Throughout this study, all experiments have been made with type A botulinus toxin, in distinction to the other types.From additional limited experience with types B, C and E toxin, there is no reason to believe that the different types of toxin vary in their action except in their rate of absorption, in speed of destruction in the body and in quantity necessary to produce poisoning.

The action of botulinum toxin on motor‐nerve filaments

“…Botulinum toxin does not impair conduction in motor-nerve trunks (Bishop & Bronfenbrenner, 1936;Guyton & MacDonald, 1947). This was confirmed for A, B and C fibres of the cat's excised phrenic, sciatic, and thoracic vagus nerves, when exposed to 104 LD5I/ml.…”

“…However, nodes of Ranvier in motor nerve filaments possess no known specialization which would make them exclusive targets for the action of botulinum toxin. Dun (1951) Guyton & MacDonald (1947), implies a slow rebuilding of this hypothetical substance.…”

Supersensitivity of skeletal muscle produced by botulinum toxin

“…As described by Guyton & MacDonald (1947) it was observed that the neuromuscular block produced by a single dose of botulinum toxin reached its maximum in about 5 days and thereafter remained at a constant level for a period of several months.…”

Unmasking, After Cholinergic Paralysis by Botulinum Toxin, of a Reversed Action of Nicotine on the Mammalian Intestine, Revealing the Probable Presence of Local Inhibitory Ganglion Cells in the Enteric Plexuses

“…In rabbits the toxin was injected locally into the wall of an intestinal segment, which was examined later after the death of the animal from a spread of intoxication. Further information was gained by studying the response of these poisoned segments to nicotine; with this drug it is possible to stimulate the same ganglion cells in the intestine as are involved in the mediation of peristaltic reflex activity, and the extinction of the motor response to nicotine can therefore be used equally well as an index of the paralysis in the myenteric plexus.Botulinum toxin has a selective affinity for cholinergic nerve endings, and produces effects resembling denervation (Guyton and MacDonald, 1947;Ambache, 1949Ambache, , 1951. It is generally assumed that the nerve fibres originating from the cells of the myenteric plexus are cholinergic.…”

“…Botulinum toxin has a selective affinity for cholinergic nerve endings, and produces effects resembling denervation (Guyton and MacDonald, 1947;Ambache, 1949Ambache, , 1951. It is generally assumed that the nerve fibres originating from the cells of the myenteric plexus are cholinergic.…”