514 5. QUINONES 



effects accurately, but there seems to be a good deal of disagreement as to 

 what the naphthoquinones do. Menadione and menadiol-diP injected in- 

 travenously into rabbits produce definite signs of central excitation (Foster, 

 1940; Fromherz, 1941), and hydrolapachol possibly exerts similar effects 

 in dogs and man (Wiselogle, 1946 a). On the other hand, Shimkin (1941) 

 never observed central stimulation in mice given 1,4-naphthoquinone or 

 menadione, and Smith et al. (1943) found only evidence of depression in 

 rats given menadiol-diP. These may be species differences but the general 

 lack of a consistent picture of response makes impossible a discussion of 

 the central actions of the naphthoquinones. 



Actions on the Circulation 



The quinones in toxic doses generally dilate the blood vessels, which is 

 often obvious from the increased peripheral flow and the temperature rise 

 in the extremities, and may damage the vessels in certain organs, such as 

 the lungs and kidney (page 519). The effects on the blood pressure have been 

 studied fairly thoroughly because it was thought at one time that the hypo- 

 tensive activity might be clinically useful. Most of this work was done 

 between 1942 and 1947, and was based on the demonstration by the Ja- 

 panese workers in 1934 that the quinones can often block the pressor effects 

 of the catecholamines (page 502). It was also known that menadione causes 

 a progressive fall in the blood pressure of rabbits (Ansbacher et al., 1942). 

 The first study of the quinones in hypertensive animals was undertaken 

 by Friedman et al. (1942) at the Mt. Sinai Hospital, on the assumption that 

 the quinones inactivate certain pressor amines. Rats made hypertensive 

 by wrapping the kidneys were given various quinones subcutaneously and 

 it was found that the blood pressure could be reduced to normal levels. 

 When the administration is discontinued, the pressure rises again, and this 

 cycle can be repeated several times. There is no effect on the blood pressure 

 of normal rats at the doses used. The active compounds are p-xyloquinone, 

 thymoquinone, trimethyl-p-benzoquinone, and sodium rhodizonate. The 

 effect is not immediate and requires 3-5 days to reach a maximum. It was 

 shown later (Oppenheimer et al., 1944) that similar effects are exerted 

 by 1,4-naphthoquinone, menadione, and l,2-naphthoquinone-4-sulfonate, 

 whereas juglone and 3-methylmenadione are inactive. However, the toxic 

 effects of these naphthoquinones were considered to limit their clinical use- 

 fulness. Injections of 5-10 mg menadione into hypertensive rats cause a 

 fall in the blood pressure which is maximal around the 4th day, and after 

 the injections are stopped the pressure rises again (Schwarz and Ziegler, 

 1944). 



It was thought at this time that the ischemic kidney releases pressor 

 amines which might be inactivated by the quinones. The failure to exert a 

 hypotensive action in normotensive rats at the doses employed seems to 



