100 ASYMMETRIC ASALYSIS 



SECTION I 



ANALYSIS OF THE MECHANISM OF TOXIC 



ACTION 



A. TOXIC ACTION OF THE OPTICAL ISOMERS OF NICOTINE 



A Case of Identical Mechanism of Action in the Two 

 Optical Isouters. Pictet and Eotscliv, in 1904, prepared 

 pure dextrorotatory (unnatural) nicotine, tested its tox- 

 icity on rabbits and guinea pigs, and ascertained that it 

 was less toxic than the natural 1-nicotine. They ex- 

 pressed the view, which subsequently was adopted by a 

 number of authors, of a different mechanism of toxic 

 action liy the dextro and by the laevo isomers, the symp- 

 toms of poisoning having been found different. 



Maclit (1929) studied the pharmacological synergism 

 of stereoisomeric nicotines. He found that the toxic 

 action of a mixture of the 1- and dl- forms was stronger 

 than the additive action of these isomers. The con- 

 clusion that he reached then was that "an individual 

 cell may possess receptor groups of a laevo and dextro 

 type, and a mixture of two stereoisomers would thus have 

 a double point of attack in place of a single one, in case 

 only one of the optic isomers was used." The three fol- 

 lowing points in the work of Macht are open to criti- 

 cism. First, his important final conclusion is based on 

 a very small number of experiments. Then, the author 

 did not attempt to obtain a concentration-toxicity curve 

 which would allow one to make some quantitive calcula- 

 tions. Moreover, dl-nicotine is not the most suitable for 

 such experiments, as it usually contains some hydronico- 

 tine which influences the physiological effect (Gause, 

 1936) ; only the purest dextro nicotine obtained by re- 

 peated crystallizations with laevotartaric acid should be 

 used. 



In the experiments of Gause and Smaragdova (1939) 

 the dextro isomer, in accord with the data of Pictet and 

 Eotschy, was found less poisonous than the laevo form. 



