70 ROLAND FISCHER 



tance whether the compound is cationic (basic) or anionic (acidic) in nature 

 (non-ionic compounds have no affinity for wool). Some of the environmental 

 factors are: temperature, the presence and concentration of salts, pH, the de- 

 gree of dissociation (the higher the degree of dissociation, the lower the affinity 

 of the compound for wool), the number and kind of reactive groups, such as 

 OH, NH 2 , etc. 



(2) In addition, there is a finer structural configuration which will determine 

 specific pharmacological action. 



The affinity for wool of a substance appears to be a prerequisite for a certain 

 type of biological activity; on the other hand, affinity for wool in itself does 

 not imply a specific pharmacological activity. 



IV 



Relation between Affinity for Wool of a Compound and its 



Biological Activity 



Wool as a General Model for Cholinesterase 



We have pointed out that there is a relation between the affinity of a drug 

 for wool and the ability of the same drug to produce hallucinations. 



In the following discussion we will consider only mescaline, LAE and LSI). 

 It can be argued that mescaline in itself is not the active compound when ad- 

 ministered to human volunteers but forms compounds similar to the LSD or 

 LAE structure. Such a hypothesis was recently postulated (Fischer, 1955) that 

 the biosynthesis may be brought about through condensation of minute 

 amounts of mescaline with nor-adrenalin or 5-hydroxytriptamine, both recently 

 identified in the brain. Several data appear to support the above hypothesis 

 that mescaline is transformed in vivo to a compound resembling LSD in its main 

 structural features and having an affinity for wool, and that the observed phys- 

 iopathological and psychopathological properties of mescaline are due to this 

 LSD-like compound. 



The prevention of a 80y-LSD-caused psychosis, by the previous adminis- 

 tration of a structurally related substance, a potential competitive inhibitor, 

 was tried. Suitable compounds were selected from the phenothiazine series. 



It is well known that methylene blue, a phenothiazine derivative, is capable 

 of staining the ends of living nerves; that it is an analgesic, an antimalarial and 

 an antiseptic. Phenothiazine, on the other hand, is an anthelmintic and the 

 base substance of drugs with antihistaminic, fungicidal, adrenolytic and anti- 

 emetic activity. In addition these compounds cause a fall in body temperature, 

 display a ganglionic blocking as well as a curarizing action and even some quini- 

 dine-like action. We found that methylene blue, N-(2-diethylamino-n-propyl)- 

 phenothiazine (Parsitan), 3-chloro-10-(3-dimethylaminopropyl) phenothiazine 

 (Largactil) and (8-diethylaminoethyl-N-phenothiazine (Diparcol) display a 



