In order to establish the influence of temperature upon the effect of varying doses of strychnin injected into frogs, the animals must be kept under observation for several days and at various definite degrees of temperature. Statements that the animal was kept "cold," "at room temperature," or "warm" are insufficient. With a certain dose tetanus may result constantly at 30° C. yet never appear at 21° C., and either of these temperatures might be described as warm, when compared to a room temperature of 15° C. Furthermore an animal may apparently fail to respond in the cold to an injection of certain doses of strychnin and yet be found in tetanic convulsions the next day. That an animal may have late, long lasting, or strong tetanus while kept at such a low temperature as 5° C. after an injection of a dose of strychnin smaller than 0.01 of a milligram per frog emphasizes the fact that great caution must be exercised in formulating laws as to the influence of temperature on drug action.
The main results of this investigation may be summarized as follows: Doses of strychnin amounting to 0.0006 of a milligram per gram of frog will cause tetanus at all temperatures between 5° C. and 30° C., although at low temperatures the tetanus may appear late. A dose of 0.0003 of a milligram per gram of frog will frequently produce tetanus at 5° C. as well as at 30° or 27° C., but may nevertheless fail to produce any reaction at such an intermediary temperature as 21° C. Smaller doses, 0.0002 of a milligram per gram, will cause tetanus in the cold but not at high temperatures.
It may be stated in general that in frogs kept at low temperatures the tetanic state sets in later, continues longer, and each tetanic attack is of longer duration, while in the interval between the attacks the state of tonus is higher and the animals are more irritable than when they are kept at higher temperatures.