[Claude Bernard and nicotinic receptors: from the neuromuscular junction to tobacco weaning]. / Claude Bernard et les récepteurs nicotiniques : de la jonction neuromusculaire au sevrage tabagique.

ABSTRACT

Claude Bernard (1813-1878) was fascinated by the pharmacological mechanisms of poisons. In particular, using a huge amount of ingenious and robust experiments, he demonstrated the peripheral toxic action of the natural compound curare. His work generated controversies in a period where scientific methodology and technical development followed the progression of concepts and ideas. From his intense debates with Albert Vulpian emerged the location of curare's toxicity at the neuromuscular junction. These two fascinating scientists could not imagine how important were these discoveries which allowed John Langley to propose the concept of receptor early in the 20th century. At the same time, the German immunologist Paul Ehrlich suggested that these receptors could be targeted by so-called "magic bullets", i.e., drugs that act on receptors, in order to treat patients. The molecular substrate of curare's activity was identified many years later as the nicotinic receptor of the motor end-plate. We now have curare molecules belonging to various chemical families that block receptors during anaesthesia. Suggamadex is the antidote for two of them, a drug that Claude Bernard perhaps dreamt of. We also have the recently marketed varenicline that acts as a partial agonist of nicotinic receptors in the central nervous system to treat patients from tobacco addiction. This rich story shows that biomedical research needs collaborations, imagination, perspicacity but also all results that it can have many years later, therefore challenging researchers about consequences of their discoveries.