In considering the action of drugs on muscle, the first point which comes clearly out is that the action of a drug on the muscle is not absolute, but merely relative. Thus veratrine and salts of barium are not to be regarded as absolute muscle-poisons - they are only poisons under certain conditions of quantity and of temperature. An exceedingly small dose of veratrine, instead of acting as a poison to muscle, acts rather as a food, and restores it when exhausted. Caffeine likewise in small doses has a restorative action, while in large doses it is a powerful poison. Veratrine and barium in moderate doses and at moderate temperatures are powerful muscular poisons, but at low temperatures and at high temperatures their action is to a great extent, or even completely, abolished. Nay more, moderate quantities of barium salts at moderate temperatures are poisonous to the normal muscle, but they are restorative to the muscle whose composition and functions have been already altered by rubidium. Acids and alkalis also produce an effect on muscle, but their effect depends upon whether they are applied to the normal muscle or to one previously treated with a substance having an opposite reaction.

It is evident, then, that the whole question of the action of drugs on muscle is one involving the relation of the drug to the muscle at the time of application, and we must expect that if the temperature is different from the normal, or if the composition of the muscle should vary, the action of the drug will vary likewise. Now the composition of all the muscles in the body is not the same, as has been shown by Toldt and Nowak,1 and the composition of the ash obtained by the combustion of different animals is also different, as has been shown by Lawes and Gilbert.2 We may therefore expect that muscular poisons will not act alike at the normal temperature and in febrile conditions, nor alike upon all the muscles of an animal; nor will they always have the same action upon different animals - the relations being different, the effects will be different. The effect of poisons upon muscles will also vary according to the chemical composition of the tissue at the time. This composition may probably, to a certain extent, be altered by feeding - at least as far as regards the proportions of inorganic ingredients. We know that the quantity of sodium chloride in the body can be increased, for if an animal be fed with a larger quantity of salt than usual, it does not at once begin to excrete, but stores it up for two or three days, and then the excretion increases. After the administration of the salt has been stopped the excretion continues large for two or three days, and then returns again to the lower standard. It seemed probable that similar retention would take place with potash, and if this were so, we might expect to counteract to a great extent the effect of barium by feeding an animal on potash for some time before administering the barium. On trying this, Cash and I have found that this is the case to a certain extent, and although we have not been able completely to counteract the effect of a large dose of barium so as to prevent death from a lethal dose, we have been able to modify and diminish its action by the administration of potash for several days previously, so that the characteristic symptoms of barium poisoning do not occur until some hours after they would otherwise do so, and thus life is prolonged though not preserved.

1 Quoted by Seegen, Wien. Akad. Ber. lxiii. Abt. ii., 11-43.

2 Proc. Boy. Soc, xxxv., p. 344.