Invited review: Anticholinesterases: dramatic aspects of their use and misuse.
While the lore of anticholinesterases (antiChEs), particularly physostigmine and its natural source, the Calabar bean, is a subject of ethnomedicine and predates our scientific era, the pharmacological development of physostigmine analogues and related agents and of the antiChEs of the organophosphorus (OP) type, is a matter of the last two centuries; this development has reached an exponential character in the last fifty years. This explosion relates to certain uses and misuses of these drugs and this aspect of antiChEs is the main focus of this article. Firstly, there is the matter of Senile Dementia of Alzheimer's Type (SDAT); while there are several clinical applications of antiChEs, their employment in the treatment of SDAT is the last and most intense foray in their medical history and this article will focus on the uses and misuses of antiChEs in this area. Secondly, the applied use of antiChEs as insecticides which coincided with the historical development of OP antiChEs was and is, of major significance for the agricultural economy of both advanced and underdeveloped countries, as this employment may mean the difference between life and starvation. However, there are notable dangers with this application of OP drugs, as will be emphasized in this article. Thirdly, there is the significant and tragic development of the OP drugs as warfare agents and tools for terrorists and rogue states and this article will discuss the several types of toxicity of OP agents and their mechanisms, the enigma of the Persian Gulf War Syndrome being particularly stressed. Altogether, the immense range of antiChE topics includes areas of great basic interest and of practical applications that are of significant benefit to mankind as well as of potential danger.