206 



Mr. V. H. Veley aud Dr. A. D. Waller. [Nov. 23, 



chloroform at the temperatures 19° and 30° and gives for ether a coefficient 

 of 2-0 for a rise of 10°.* 



None of these observations have been definitely addressed to the question 

 w^hether or no the pharmacodynamic action of drugs obeys the laws of 

 chemical action in its relation to temperature, although obviously they point 

 in that direction. 



The following observations have been made as carefully as possible by 

 methods already described in previous communications. In preliminary 

 experiments we determined the most convenient concentrations to afford us 

 a sufficient number of observations at different temperatures within the range 

 of 7° to 27°. In all cases the effects were markedly increased by rise of 

 temperature ; the degree of correspondence will be evident from the details 

 of observations given below. Within the range of 7° to 27° the temperature 

 coefficient of increase in, e.g., the case of quinine {vide, infra), comes out as 

 2"52 per 10°. An upper limit is fixed by the heat coagulation of the 

 muscular substance. The lower limit appears to be that at which chemical 

 combination of this peculiar character is suspended. It varies for different 

 drugs, e.g., in the case of the powerful drug aconitine the poisonous effect is 

 completely inhibited at a temperature of about 7°. As will be shown below, 

 this inhibition is temporary. 



The question whether the acceleration and retardation of a toxic effect by 

 higher or lower temperature are really of a chemical nature, and not merely 

 by reason of differences of physical diffusion, is very easily answered. 



Taking a strength of drug and a low temperature such that cliemical 

 action (but not diffusion) is practically suppressed, and subsequently placing 

 in normal saline the muscle in which diffusion (but not combination) of the 

 drug has taken place, we now find the characteristic effect of tlie drug to 

 manifest itself, e.g., No. 631 (fig. 16). And apparently the rate of this 

 delayed effect is not sensibly different from the rate of an undelayed effect, 

 which goes to sliow that in an ordinary experiment where rate of diffusion 

 and rate of cliemical cliangc are to be thought of, tlic former is negligible in 

 comparison witli the latter. 



As a preliminary to the study of tlie effect of temperature upon the rate 

 of action of drugs upon muscle, we naturally took observations of the effect 

 of variations of temperature upon contraction in tlie absence of drugs. 

 This brouglit out one very definite and, we lielicve, important point. 



As is well known, contractility sulisists between an upper and lower 



limit of temperature, and it is usually considered that the upper limit is 



* "The Com para tive I'owcr of Alcoliol, I'Xlier, and ( 'lilorofdini, etc.," 'Roy. Soc. Proc.,' 

 vol. R], 15, p. 545, 1009. 



