324 



Messrs. J. Mcintosh and P. Fildes. 



of this solution - 2 c.c. were injected into the cerebrospinal fluid of a rabbit 

 weighing 500 grm., through the posterior occipito-atlantoid membrane. The 

 effect of the injection was to produce convulsions immediately, and death the 

 next day. A second rabbit (800 grm.) received - l c.c. and was found to be 

 paralysed on the following day. As a control, 0"2 c.c. of saline solution was 

 shown to be innocuous. It thus follows that about 0*0005 grm. of 

 neosalvarsan is the toxic dose to a rabbit of 800 grm. weight when injected 

 into the cerebrospinal fluid. It may be assumed that the drug is rapidly 

 absorbed from the cerebrospinal fluid into the brain and is there fixed as in 

 our experiment conducted in vitro. Thus salvarsan may be said to be as 

 much " organotropic " to the brain as to the liver, but this effect is not 

 apparent after its therapeiitic administration in the ordinary manner. 



The inability of salvarsan to penetrate into the brain explains the lack of 

 success which often attends the treatment of syphilitic lesions of the brain, 

 and in particular the parenchymatous varieties (dementia paralytica and 

 tabes dorsalis). 



We next considered whether this inability might be due, in some measure, 

 to the rapid fixation of the drug by the liver and kidneys and its removal 

 from the blood. 



We have indeed found, experimentally, that the blood is practically free 

 from arsenic two days after an injection, as shown in the following experi- 

 ment : — 



Experiment 7. — Four rabbits were injected intravenously, each with 

 € - 15 grm. of neosalvarsan. They were killed 3, 6, 24, and 72 hours after 

 the injection. Specimens of blood were collected and the animal transfused 

 with saline to remove the blood from the organs. The blood and organs con- 

 tained the following quantities of neosalvarsan : — 





Rabbit A, 

 3 lvrs. 



Babbit B, 

 6 hrs. 



Babbit C. 

 24 hrs. 



Babbit D. 

 72 hrs. 



Brain (c«. 10 grm.) 



Liver (10 grm.) 



Blood (25 c.c.) 



? trace 

 O005 

 -003 



Grammes of 



? trace 



O0075 



-0006 

 ; 



neosalvarsan. 

 O 



0012 

 0O004 







00025 

 



We next endeavoured to satisfy the affinity of the liver and kidneys for 

 arsenic by repeated injections of neosalvarsan, in the hope that a sufficient 

 content would be maintained in the blood to allow of penetration into the 

 brain. 



Experiment 8. — Three rabbits were injected, each twice daily for four days 



