PHYSIOLOGY, PHARMACOLOGY, AND TOXICOLOGY 389 



Table 34. LD 50 of Several Pyridine Derivatives for 50-100 gm 

 Rats by Subcutaneous Injection 



to be about double this. By contrast the closely related alkaloid, arecoline, 

 has a subcutaneous lethal dose for mice of 0.065 gm/kg. 102 



O 



^ ^N^ 



■N 

 I 

 CH 3 



Arecoline Nicotine 



Minimum lethal doses have also been determined for niacin intravenously 

 for a number of species and nicotine was similarly assessed in parallel 

 experiments, 103 with the results shown in Table 35. 



Table 35. Intravenous Toxicity of Sodium Nicotinate and Nicotine 



Lethal Dose (mg/kg)- 



Species Nicotine Sodium nicotinate 



White mice 0.8 4500 



Rats 1.0 3500 



Guinea pigs 4.5 3500 



Death from niacin, as from nicotine, follows severe clonic convulsions. 

 Other symptoms associated with niacin toxicity include generalized 

 paralysis, depressed respiration, and cyanosis, death generally occurring 

 in from 12 to 36 hours. 



Attention should also be called to the fact that large but sublethal 

 doses of pyridine derivatives may have a growth depressing effect by 

 virtue of the fact that they are generally excreted as INT-methyl deriva- 

 tives, and they may thus draw critically on the available methyl group 

 supply of the body. 



Choline. The pharmacological effects of choline have been well known 

 for some time 104 and choline chloride has found some use as a therapeutic 

 agent. It exerts a muscarine effect peripherally, stimulating parasym- 

 pathetic endings, and also a nicotine effect, stimulating and paralyzing 



