XII. PHARMACOLOGY 571 



considerable atrophy of the epitheUum. The buccal mucous membrane may 

 disappear entirely in some areas with grayish ulcerations which are loaded 

 with microorganisms. Cysts filled with mucus and inflammatory material 

 and, in advanced cases, ulcers are found in the colon. Chromatolysis of 

 ganglion cells in the brain and, in some cases, myelin degeneration of 

 peripheral nerves can be observed. Peripheral blood may show either 

 microcytic or macrocytic anemia. Bone marrow appears to have been 

 studied but little . 



The specificity of these pathological changes in relation to possible con- 

 comitant deficiencies of other essential nutrients has been discussed else- 

 where (p. 553). The "pellagra" of Africans, as characterized by the Gill- 

 mans," almost certainly is compHcated by other deficiencies, since it does 

 not respond to nicotinic acid but does respond to certain materials which 

 contain high-quahty protein. The extensive pathology of this severe nutri- 

 tional disease has been described thoroughly by the Gillmans." 



XII. Pharmacology 



J. M. HUNDLEY 



A. TOXICITY 



Both nicotinamide and nicotinic acid are quite non-toxic, there being a 

 ratio of at least 1:1000 between the effective therapeutic dose and the 

 toxic dose. 



1. Rats and Mice 



The LDso's of nicotinic acid (sodium salt when given parenterally) and 

 nicotinamide range from 3.5 to 5 g. per kilogram subcutaneously and 5 to 

 7 g. orally. Nicotinamide is almost twice as toxic as nicotinic acid.^'^ The 

 methyl ester of nicotinic acid injected into mice was tolerated at a level of 

 1.0 g. per kilogram, whereas the methoiodide of this compound was fatal 

 at 0.6 g. per kilogram. The methyl ester of N^-methyltetrahydronicotinic 

 acid (arecohne) was fatal at a dosage of 0.065 g. per kilogram.^ N^-Methyla- 

 tion of nicotinic acid and related compounds does not result in a consistent 



" J. Gillman and T. Gillman, Perspectives in Human Malnutrition. Grune & 

 Stratton, New York, 1951. 



1 K. K. Chen, C. L. Rose, and E. B. Robbins, Proc. Soc. Exptl. Biol. Med. 38, 241 

 (1938). 



2 K. Unna, J. Pharmacol. Exptl. Therap. 65, 95 (1939). 



' F. G. Brazda and R. A. Coulson, Proc. Soc. Exptl. Biol. Med. 62, 19 (1946). 

 * R. Hunt and R. R. Renshaw, /. Pharmacol. Exptl. Therap. 35, 75 (1929). 



