784 6. ARSENICALS 



The drug most commonly used for central nervous system syphilis before 

 penicillin was tryparsamide, on the basis that it seemed to penetrate better. 

 An interesting study was made by Hawking et al. (1937) of the trypanocidal 

 activities in the cerebrospinal fluid after the administration of tryparsamide 

 intravenously to patients. The activity is considerable at 14 hr, maximal 

 at 40 hr, and inappreciable by 80 hr; the total arsenic estimated chemically 

 does not parallel this, being maximal at 14 hr but falling rapidly during 

 the next 24 hr. Only a small fraction of the arsenic present in the cerebro- 

 spinal fluid is in the active form — around 3% at 14 hr, 18% at 40 hr, 

 and 5% at 60 hr. If trivalent arsenicals are used, much lower cerebrospinal 

 fluid concentrations are achieved as determined by trypanocidal activity. 

 It may be that penetration occurs in the pentavalent form, which must 

 then be reduced for parasiticidal activity. In any event, the relative lack 

 of central nervous system toxic reactions to the arsenicals, when a potent 

 effect might be expected on a metabolic basis, must be in large part due 

 to this failure to penetrate readily. It is also interesting that skeletal muscle 

 does not take up arsenicals readily (Table 6-18) (Beck and Gillespie, 1954). 

 Whether this is due, as with nerve, to the more critical permeability prop- 

 erties of excitable tissue is not known, but the myocardium does not ex- 

 clude the arsenicals so effectively. 



Intracellular Sites of Binding 



The interesting problem of the location of the arsenicals within the cells 

 following uptake has scarcely been considered. When radioarsenite is 

 injected into guinea pigs 8 times over 4 days, the activity appears in var- 

 ious tissue fractions (see accompanying tabulation) (Lowry et al., 1942). 



Thus the bulk of the arsenic is in the protein fraction, except for serum. 

 It would be interesting to know whether any arsenic is truly attached to 

 lipids, or whether the small amounts observed result from slight protein 

 impurities; also whether that found in the acid-soluble fraction might 

 correspond to arsenate taken in through arsenolysis reactions. It was 



