RT Journal Article
SR Electronic
T1 TRYPANOCIDAL ACTIVITY AND ARSENIC CONTENT OF THE CEREBROSPINAL FLUID AFTER ADMINISTRATION OF ARSENIC COMPOUNDS
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 157
OP 175
VO 59
IS 2
A1 F. HAWKING
A1 T. J. HENNELLY
A1 J. H. QUASTEL
YR 1937
UL http://jpet.aspetjournals.org/content/59/2/157.abstract
AB 1. A method is described of examining in vitro the trypanocidal activity of the cerebrospinal fluid after the intravenous injection of arsenic compounds. Fluids withdrawn before the administration of arsenicals, or from patients during treatment with malaria, have no trypanocidal activity. 2. Intravenous injection of 3 grams tryparsamide leads to the appearance of trypanocidal activity in the C.S.F. This is considerable at 14 hours, maximal at about 40 hours and becomes almost inappreciable after 80 hours. 3. After administrations of tryparsamide, the total arsenic content of the C.S.F. (estimated chemically) does not run parallel to the trypanocidal activity; it is maximal at 14 hours and falls rapidly during the subsequent 24 hours. Comparison of the total arsenic content with the activity indicates that only a portion (1 to 25 per cent) of the arsenic is present in an active trivalent form; the average proportions are 3 per cent after 14 hours, 18 per cent after 40 hours and 5 per cent after 60 hours. 4. The other pentavalent compounds examined caused approximately the same amount of arsenic to appear in the C.S.F. as tryparsamide, but orsanine was equal or superior to tryparsamide in producing trypanocidal activity, while neocryl, etc., were practically ineffective in this respect. 5. Intravenous injection of trivalent arsenic compounds (neoarsphenamine, sulpharsphenamine, arsphenamine diglucoside, silver arsphenamine) led to the appearance of lower concentrations of arsenic in the C.S.F.; and the trypanocidal activity was slight or absent. This accords with the therapeutic inefficiency of these compounds for neuro-syphilis and sleeping-sickness. 6. In a small series of patients given tryparsamide, there was no significant difference in the arsenic content or trypanocidal activity of the C.S.F. between patients with organic lesions (general paresis) and those without organic lesions (schizophrenia and manic depressive psychosis). 7. It is suggested that the concentration of trypanocidally active arsenic in the cerebrospinal fluid depends upon (a) the rate of penetration into the brain of the compound injected; (b) in the case of the pentavalent arsenic compounds, the rate of reduction to the active trivalent form and its diffusion out into the C.S.F.; (c) the rate of deactivation of this active form by oxidation or by combination with tissue components.