COMMENTS ON THE EXCITINE-INHIBITINE HYPOTHESIS 



381 



the excitatory principle. We found that heating of the cerebrospinal fluid 

 caused the disappearance of the active substance and the same could be 

 achieved by de-proteinization with subhmate and ethyl alcohol. 



When 3 ml of the cerebral spinal fluid collected during seizure were mixed 

 with 9 ml of absolute methanol the activity was maintained. After centri- 

 fugation the supernatant was reduced to half its original volume and when it 

 was injected into the ventricle of another dog it produced seizures. 



It was found that the eff'ective agent cannot withstand temperatures above 

 40°C, and that it is unstable in acid media (pH 2-3) and in alkahne media 

 of pH 8-9. The substance is very unstable in pure oxygen and disappears 

 within 1 min; during exposure to open air it loses its activity in 1 or 2 weeks. 



Further analysis of the constitution of the excitatory agent is now going 

 on. At present we call the effective fluid "crude excitine". 



When a dose of "crude excitine" which is effective to produce seizures was 

 mixed with 2 ml of 0-2 m GABOB and introduced into the cerebral spinal 

 fluid of a dog it did not produce seizure. If such a mixture was subjected to 

 the flow of an electric current in the apparatus shown in Fig. 1, excitatory 

 activity could be found in the cathodal as weU as in the anodal fluid. 



Fig. 1. Experimental set-up for the electrophoretic separation of excitine and 

 inhibitine (see text). 



We therefore feel that the excitine-inhibitine hypothesis can be apphed to 

 the central nervous system. 



DISCUSSION 



I have named released chemical agents "excitine" and "inhibitine" on 

 some occasions, and "chemical transmitters" on others. Are they the same 

 things? In the peripheral nervous system they are not the same. For instance, 

 in a motor nerve in skeletal muscle there are three patterns of tissue: 



(1) The nerve fibre. 



