The actions of edrophonium [ed-row-FOE-nee-um] are similar to those of neostigmine, except that it is more rapidly absorbed and has a short duration of action of 10 to 20 minutes (prototype short-acting agent). Edrophonium is a quaternary amine and is used in the diagnosis of myasthenia gravis. Intravenous injection of edrophonium leads to a rapid increase in muscle strength. Care must be taken, because excess drug may provoke a cholinergic crisis. Atropine is the antidote. F. Tacrine, donepezil, rivastigmine, and galantamine As mentioned above, patients with Alzheimer's disease have a deficiency of cholinergic neurons in the CNS. This observation led to the development of anticholinesterases as possible remedies for the loss of cognitive function. Tacrine [TAK-reen] was the first to become available, but it has been replaced by the others because of its hepatotoxicity. Despite the ability of donepezil [doe-NEP-e-zil], rivastigmine [ri-va-STIG-meen], and galantamine [gaa-LAN-ta-meen] to delay the progression of the disease, none can stop its progression. Gastrointestinal distress is their primary adverse effect (see p. 102). VI. Indirect-Acting Cholinergic Agonsists: Anticholinesterases (Irreversible) A number of synthetic organophosphate compounds have the capacity to bind covalently to acetylcholinesterase. The result is a long-lasting increase in acetylcholine at all sites where it is released. Many of these drugs are extremely toxic and were developed by the military as nerve agents. Related compounds, such as parathion, are employed as insecticides.