Unique Insights into the Actions of CNS Agents: Lessons from Studies of Chlorpyrifos and Other Common Pesticides

The development of CNS drugs has been the most challenging task in drug design. Only an abysmal one percent of nervous system drugs tested in human clinical trials ever reach market. This is largely attributable to the difficulties in both identifying appropriate targets and in understanding the toxicology, pharmacology, and pharmaceutical properties of therapeutic compounds. Pesticides have not attracted much attention in the field of CNS drug design. However, the toxicological and molecular actions of certain pesticides, such as chlorpyrifos and pyrethroids, have been well studied. Furthermore, recent epidemiological data have provided important insights into the actions of pesticides in the human brain. Therefore, in this review we seek to examine and summarize the toxicological and molecular actions of common pesticides, organophosphates and pyrethroids. We will also summarize and compare the effects of common pesticides on the neurological functions in animals and in humans. Common pesticides have been shown to act on molecular targets such as the serotonin receptors, brain-derived neurotrophic factor (BDNF), and the transcription factor CREB. Likewise, pesticides can affect multiple neurological functions, such as motor coordination, habituation, attention, cognition, and psychomotor development. A comprehensive review of the toxicological and molecular roles of pesticides in the CNS might provide insights into the actions of CNS agents.