WOOL AS AN INDICATOR OF NEUROPHARMACOLOGICAL ACTIVITY 



73 



lyzed by an enzyme. In the nerve membrane a suitable system with a sufficiently 

 high reaction velocity is represented by the acetyl choline-cholinesterase system. 



This is, so far, the fastest enzymic reaction known in animal cells, since one mole 

 of enzyme can split 2.10 7 moles of substrate per minute. According to Hestrin 

 (1950), the equilibrium between the ester and its hydrolytic products 



acetylcholine + H 2 i=± acetic acid + choline 



is shifted to the left with decreasing pH. Thus under more acid conditions more 

 ester will be formed by the enzyme, whereas in a more alkaline environment 

 hydrolysis will be favored. Taking into account the dissociation constant of 

 acetic acid, pK a = 4.7, it is clear that the assumed buffer system will work best 

 around pH 5. We would like to mention in this context that our affinity for wool 

 measurements have been carried out at pH 5-5.2, i.e. very close to the iso-elec- 

 tric point of wool (pH 4.9-5). 



Since quaternary ammonium compounds display the highest affinity for wool 

 protein and, on the other hand, we may regard wool protein as a model for cho- 

 linesterase, there are two points to be considered; first, the adsorption of the 

 quaternary appears to interfere with the normal enzyme function either by 

 neutralizing the anionic groups which may be necessary for enzyme action (this 

 is the more likely explanation) or, secondly, by a steric interference preventing 

 the action of the enzyme by covering too much of its surface. 



Limitations when Using Affinity for Wool as an Indicator of 



Biological Activity 



In a series of adrenergic blocking agents not available for commercial use, 

 and which were obtained by the McNeill Laboratories, Philadelphia, through 

 the courtesy of Dr. Ansel P. Swain, we measured the affinity of the following 

 six compounds for wool. 



Affinity for 1 gm. 



of wool in mMoles 



x 10 2 



Compounds 



Mol. Weight 



5.3 



N.N-Diethyl l-(3-indolylmethyl) is;>- 

 nipecotamide hydrochloride 



C 19 H 27 N :i O. 



HC1 



Mol. Wt. 



349.9 



HC1 



i NH / 



active 



