FORTY-FIVE years after Beecher and Todd 1 first described an increase in mortality associated with the use of D-tubocurarine, anesthesiologists are still learning how best to use neuromuscular blocking agents (NMBAs) and their antagonists. Practices regarding antagonism of residual neuromuscular block vary based on the country of practice, type of anesthetic practice, and individual clinician p...

Organophosphate and carbamate insecticides are widely detected in surface waters of the western United States. These chemicals interfere with acetylcholine-mediated synaptic transmission in the nervous systems of fish and other aquatic animals via the inhibition of AChE (acetylcholinesterase) enzyme activity. Anticholinesterase insecticides commonly co-occur in the environment. This raises the ...

Organophosphate (OP) compounds are present in household and agricultural pesticides as well as in nerve agents. The toxic effects of these chemicals result from their anticholinesterase activity, which disrupts nerve junctions and parasympathetic effector sites, leading to a variety of symptoms and possible death. When the anticholinesterase agents in OP compounds reach the neuromuscular juncti...

We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer's disease (AD). Its synthesis features as the key step a novel multigram preparative chromatographic resolution of intermediate racemic huprine Y by chiral HPLC. Administration of this co...

Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. Herein, we describe the design and synthesis of a novel class of shogaol-huprine hybrids, purported to hit several key targets involved in Alzheimer's disease. The hybrids have been tested in vitro for their inhibitory activity against human acetylcholinesterase and butyrylcholinesterase and an...

Mice were administered anticholinesterase pesticides dichlorvos (DDVP) or methomyl (MET). Both DDVP and MET induced dose-dependent seizures and lethality in mice. The muscarinic antagonist atropine (ATR, 1.8 mg/kg) did not prevent seizures but diminished the lethality induced by DDVP or MET. The nicotinic antagonist mecamylamine (MEC, 1 mg/kg) affected neither DDVP-induced seizures nor DDVP- an...