QUATERNARY AMMONIUM BASES
General Statement. — The organic derivatives of ammonium are strikingly similar in their action. They produce a curare effect, i.e., paralysis of the nerve endings of striped muscle (Brown and Fraser. 1869) some also muscular tremors in frogs; and those possessing three or four methyl groups cause a muscarin effect, i,e., peripheral stimulation of the cardiac vagus; and a nicotin action, i.e., paralysis of sympathetic ganglia, The curare effect evidently depends on 5-valent nitrogen; or rather, on the stereochemic configuration; for the same characteristic is shown by the corresponding phosphorus, arsenic and antimony compounds. The various actions differ in degree with the various derivatives — i.e., the methyl and ethyl ammoniums—in ways which are not easily explainable by their constitution {Burn and Dale, 1915).
TETRA-METHYL AMMONIUM CHLORID
This produces a typical curare- effect in mammals and frogs. Ammonium convulsions occur in mammals, but not in frogs, being prevented in the latter by the more powerful curare paralysis. The circulatian shows a fall of blood pressure, generally with slowing of the heart, by peripheral vagus stimulation and peripheral vasomotor depression. The respiration is temporarily paralyzed by intravenous injection; in decerebrated animals, this is preceded by respiratory stimulation. The paralysis is due to a curare effect on the phrenic nerves (Marshall. 1913). Loevenhart, 1914, however, believes that the respiratory action is entirely central; 1.e., primary stimulation and later depression of the medullary centers.
TETRA-ETHYL AMMONIUM CHLORID
In frogs, this produces irregular muscular contractions and tremors; first fibrillary, then tonic. With larger doses, these are succeeded by paralysis. Both actions are seated in the muscle-nerve endings. Mammals also show increased excitability and depression of the endings. Rabbits exhibit dyspnea, tremors, convulsions, and arrest of respiration. In distinction to tetra-methyl ammonium, there is no direct action on the circulation; the respiratory effects are also smaller (Marshall, 1914). Burn and Dale, 1915, found no curare or muscarin action, but a good nicotin effect.
METHYL-ETHYL AMMONIUM COMPOUNDS
The actions of these are, on the whole, intermediate; but without definite ratio to the alkyl radicals (Marshall, 1915; Burn and Dale, 1915).
NICOTIN
General Statement. — Nicotin, the chief alkaloid of tobacco, has no therapeutic importance, but considerable scientific and toxicologic interest. Both the central and peripheral actions are important; both consist in short stimulation, followed by depression or paralysis. Centrally, small doses cause chiefly a respiratory stimulation; larger doses produce convulsions of the medullary type. The action is enormously rapid, approaching hydrocyanic acid. Peripherally, nicotin paralyzes all autonomic ganglia, parasympathetic as well as sympathetic. The paralysis may be preceded by stimulation. The most important effects are on the circulatory and gastro-intestinal systems. It has also a curare action on muscle-nerve endings.
The effects of tobacco are due practically solely to its nicotin. Limited tolerance to the acute toxic effects is soon acquired, after which it acts
