Re: Can anyone describe how the drug Phenamil causes erthrocytes to lyse?

A search of the PubMed and of Google web sites did not yield a scientific 
study that directly answers your question.  I was not able to find any 
evidence that phenamil does cause red blood cell lysis, or hemolytic 
anemia.  In addition, I was unable to find any evidence that the related 
compound, amiloride, causes red blood cell lysis.  Therefore, 
unfortunately, I can't offer you any insight into explaining your results, 
other than to inquire whether you have controlled for the solvent that you 
have used to dissolve the phenamil, as it is insoluble in water.

Now, for the sake of scientific inquiry, let’s hypothesize that phenamil 
causes hemolysis as the result of altered levels of copper in the blood.  
Although I was unable to find any evidence that phenamil alters blood 
copper levels, here is the basis for the hypothesis.

Phenamil inhibits sodium ion absorption, and thus is useful in the 
treatment of cystic fibrosis (Kunzelmann and Mall 2001).  Copper uptake in 
some cells occurs, at least in part, via sodium channels and is blocked by 
phenamil (Grosell and Wood 2002).  If phenamil were able to sufficiently 
increase blood copper levels, secondary to its effects on sodium and 
copper ion absorption, then this could cause hemolysis, as high blood 
levels of copper (e.g., occur in Wilson’s disease) can cause lysis of red 
blood cells (Lovstad 1982, Saenko et al. 1990).  See also, the Merck 
Manual web site 
(http://www.merck.com/pubs/mmanual/section1/chapter4/4j.htm)


It seems very unlikely to me that this mechanism could explain your data.  
Most importantly, I encourage you to keep thinking about this problem.  
You may have discovered an intersting property of the drug, which may be 
useful in the study of red blood cell ion transport mechanisms.  Good luck.



REFERENCES
Kunzelmann, K. and Mall, M.  (2001)  Pharmacotherapy of the ion transport 
defect in cystic fibrosis.  Clinical and Experimental Pharmacology and 
Physiology 28, 857-867.

Lovstad, R.A.  (1982)  The protective action of ceruloplasmin on copper 
ion stimulated lysis of rat erythrocytes.  International Journal of 
Biochemistry 14, 585-589..

Saenko, S.L., Skorobat’ko, O.V. and Yaropolov, A.L.  (1990)  Interrelation 
between structure and protective action of normal and pathological 
ceruloplasmins during copper-induced lysis of red blood cells.  
Biochemistry international 22, 749-757.

Grosell, M. and Wood, C.M.  (2002)  Copper uptake across rainbow trout 
gills: mechanism of apical entry.  The Journal of Experimental Biology 
205, 1179-1188.