WOOL AS AN" INDICATOR OF NEUROPHARMACOLOGICAL ACTIVITY 



67 



Bovet et al. (1953) have shown that the part mainly responsible for the spe- 

 cific pharmacodynamic activity of dehydrogenated ergot alkaloids is the molec- 

 ular configuration centered at the primary NH 2 -group and its neighbourhood. 

 We can extend this observation to almost all of our compounds involved in this 

 report and compare in a deliberately oversimplified way the aforementioned 

 groups on these compounds as one factor supposedly influencing their increas- 

 ing absorption (affinity) for wool. From mescaline to methedrine: there is an 

 additional monomethyl group on the primary amino N. The third drug, LAE, 

 also has an alkylated primary amino group (monoethyl) and then a 

 three C-chain counting up to its additional N in the nucleus of the formula; the 

 latter initiates a second N— C— C— C- X -grouping; LSD, the fourth drug, 

 differs from LAE only by a higher grade of alkylation on the primary amino 

 group (di-ethyl). Hence we note that (1) a gradually higher grade of alkyla- 

 tion and (2) the presence of two "LSD-tails" (N— C— C— C--N) are among 

 the structural concomitants of our basic drugs displaying an increasing se- 

 lectivity for wool. 



The next formula, methylene blue, shows us a substance of even higher affin- 

 ity (i.e. absorption) for wool than LSD, namely 3.3 X 10~ 2 niMoles/gm. wool. 



Methylene blue; Mol. weight: 320 



Here we observe two dialkylated "LSD-tails" each of which has 4 C atoms 

 (instead of 3, as in LAE and LSD) between the primary amino group and the 

 N-atom of the ring. 



Before considering some of the structural characteristics of SKF-501, which 

 displayed the highest affinity for wool among all the compounds tested up to 

 now in this study (3.8 X 10~ 2 mMoles/gm. wool) let us draw attention to the 

 findings of Harvey and Nickerson (1953), which show that compounds of the 

 Dibenamine type, including SKF-501, might occur in the body in their ethyl- 

 enimonium form. These authors also have shown that such a form exerts the 

 same adrenergic blocking activity as the original configuration. 



Increasing absorption (higher degree of specificity for wool protein) of basic 

 (cation-active) drugs is accompanied (for further factors see Fischer and Larose, 

 1952b) by the following structural features: (a) increased grade of alkylation 

 on the primary amino group, the latter which may be present as quaternary N 

 in vivo, (b) increasing number of such amino-groups, (c) increasing number of 



