168 ROBERT G. GRENELL 



(e.g. production of convulsions) and above all in the total behavioral response 

 of the organism. One example of this last effect is the difference in action of 

 two of the new "psychiatric" drugs — Frenquel and Meratran. These two sub- 

 stances are isomers. Meratran, however, is a stimulant, while Frenquel is a 

 tranquilizer and blocker of such drugs as LSD-25 (which produces hallucina- 

 tions). It cannot be overlooked, therefore, that molecular arrangement is funda- 

 mentally related to nervous activity. 



In addition, a second molecular problem has been brought up in these pre- 

 sensations of "reception." This is the problem of receptor sites — loci in the cell 

 surface, the properties of which relate to the effectiveness of molecules to which 

 they are exposed. The question, broadly, is concerned with the importance of 

 molecular size, shape and other properties in relation to the fit of the molecule 

 into a particular site (whether this be enzymatic or not). These questions are 

 raised again later in the symposium particularly by Drs. Fischer and Mullins. 

 It is clear that such properties as stimulus reception and response (including cer- 

 tain characteristics inherently part of what we call threshold) are directly and fun- 

 damentally related to certain molecular characteristics and bonding. It has been 

 proposed that the most crucial of these are molecular shape and cohesive energy 

 density. The importance of and interrelationships between the problem of mo- 

 lecular shape and size and the concepts of receptor sites has been brought out 

 in more detail by some of Dr. Mullins' considerations. He has attempted to set 

 up a hypothesis (on the basis of both logic and experiment) which could serve 

 to explain why certain substances stimulate and why others block, as well as to 

 deal with the even greater complexity of the bimodal response of neural struc- 

 tures as the concentration of a particular substance is increased. Dr. Davies 

 discussed some more classical concepts of membrane structure. Although these 

 two presentations are quite different, it is of great interest and importance to 

 future work that they can be fitted together in certain respects. Although both 

 concepts ultimately become involved with "leakiness" of the membrane, and 

 thus with changes in ion permeability, it is hard to see the mechanism in the 

 more classical approach, which would deal with the question, for example, of 

 the initiation and amplification of excitation. On the other hand, Dr. Mullins' 

 views do offer something quite specific in this regard. It is of further importance 

 that both these discussions and that of Dr. Fischer, which points out certain 

 other considerations of "membrane" binding, have given us a much more ad- 

 vanced picture of a membrane which changes structure as physiological con- 

 ditions change. As Dr. Ling pointed out, it is not impossible to fit his 

 fixed-charge hypothesis into a membrane theory such as that suggested by Dr. 

 Mullins. All of these views suggest further problems and experiments dealing 

 with separation of membrane effects from intracellular non-membrane ones; 

 the relationship of membrane effects to intracellular substrate production; the 



