ANTICHOLINESTERASES - MEDICAL APPLICATIONS OF NEUROCHEMICAL PRINCIPLES

Cholinesterases form a family of serine esterases that arise in animal s from at least two distinct genes. Multiple forms of these enzymes ca n be precisely local localized and regulated by alternative mRNA splic ing and by co- or posttranstational modifications. The high catalytic efficiency of the cholinesterases is quelled by certain very selective reversible and irreversible inhibitors. Owing largely to the importan t role of acetylcholine hydrolysis in neurotransmission, cholinesteras e and its inhibitors have been studied extensively in vivo. in paralle l, there has emerged an equally impressive enzyme chemistry literature . Cholinesterase inhibitors are used widely as pesticides; in this reg ard the compounds are beneficial with concomitant health risks. Poison ing by such compounds can result in an acute but usually manageable me dical crisis and may damage the CNS and the PNS, as well as cardiac an d skeletal muscle tissue. Some inhibitors have been useful for the tre atment of glaucoma and myasthenia gravis, and others are in clinical t rials as therapy for Alzheimer's dementia. Concurrently, the most pote nt inhibitors have been developed as highly toxic chemical warfare age nts. We review treatments and sequelae of exposure to selected anticho linesterases, especially organophosphorus compounds and carbamates, as they relate to recent progress in enzyme chemistry.