176 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



TABLE 2. Range of Effectiveness on Single Eel 

 EleUroplaques of Some Synapse Inactivating and 

 Synapse Activating Drugs 



Minimum effective 

 concentration 

 Substance '" fg per ml 



a) Compounds which inactivate the postsynaptic membrane 

 of eel electroplaques, do not depolarize, but convert the 

 all-or-nothing response of the electrically excitable 

 membrane to the gradedly responsive 

 Physostigmine 25 



</-Tubocurarine 50 



DFP* 100 



Procaine 200 



Tertiary analog of prostigmine 1000 



Flaxedilt 



A) Compounds which activate synapses of eel electroplaques. 

 The resultant depolarization secondarily inactivates the 

 electrically excitable membrane. Synaptic electrogenesis 

 still occurs 



.\cetylcholinet 5 



Carbamylcholine 10 



Decamethonium 10 



Dimethylaminoethyl acetate (DMEA)t 50 



Prostigmine 5° 



SuccinylcholineK 



* This substance causes a secondary depolarization with 

 consequent inactivation of the electrically excitable mem- 

 brane. 



t Included on the basis of the data of Chagas & Albe- 

 Fessard (39) that the action of Flaxedil is similar to that of 

 curare. These workers did not study membrane potentials or 

 graded responsiveness. Chemically Flaxedil is tri-(diethyl- 

 aminoethoxy) benzene triethyliodide. 



I In the presence of 25 ^g per ml physostigmine. 



Tl On the basis of the data of Chagas & Albe-Fessard 

 C39). who found a similarity of action with acetylcholine 

 (see note f). 



since it applies as well 10 hyperpolarizing synapses 

 and to systems containing both electrogenic types 

 (96, 97). The two major varieties of drugs are in this 

 case classified as activators or inacti\ators of synaptic 

 electrogenesis. The nature of the latter, depolarizing 

 or hyperpolarizing, is determined only by the type 

 of synapse not by the activator substance. Each major 

 group is subdivided into drugs which act nonselec- 

 tively or selectively upon either the depolarizing or 

 hyperpolarizing synapses. The interactions of drugs 

 and synapses disclose many sui)sidiary classifications, 

 both in the drugs and in synaptic membranes (99, 

 100, 108), but these need not be considered here. 



The overt manifestations of 'excitation' and 'in- 

 hibition' of the six classes of drugs in table 3 need 

 not correspond to the basic mode of achieving this 

 effect at the synaptic level. Thus, the 'excitant' ac- 



TABLE 3. Possible Combinations of Actions of 

 Synaptic Drugs 



-f indicates an effect; o, none. Diphasic actions omitted. 



TABLE 4. Cortical Synaptic Actions of Aliphatic 

 Amino Acids 



Car- 

 bon 

 No. a-amino acids 



w-ammo acn 



ids 



Glycine 



3 o 



(a-alanine) 



)-diamino acids 

 X 



X 



(/3-alanine) 

 (7-aminobutyric) 



(a-aminobu- (7-aminobutyric) (2,4diamino- 

 tyric) butyric) 



50 -- o 



(Norvaline) (a-amino ly-valeric) (Ornithine) 

 6 o +++ + 



(Norleucine) (e-amino caproic) (Lysine) 

 8 X -f-|- + + X 



(co-amino caprylic) 



Symbols: — to indicate increasing blockade of 



excitatory synapses which leads to overt inhibitory' action; 

 + to -|- + -|--|- represent increasing blockade of inhibitory 

 synapses leading to 'excitatory' effects; o, compound not 

 active; X, not available or not tried. 



tions of the two conxulsant agents, strychnine and 

 pentylentetrazol, are produced by entirely difTerent 

 fundamental processes (166). The similarities in 

 overt cfl'ects arise from the conditions that prevail in 

 systems which contain many synapses and of both 

 tvpes. It is then likely that an activity is a mixture 

 involving both excitatory and inhibitory synaptic 

 actions, and the study of the central nervous system 

 has revealed many examples of this. Blockade of 

 synaptic activity thus becomes a positive act, en- 

 hancing or diminishing overt manifestations such as 

 motor activity, depending upon which type of 



