Physostigmine (also known as eserine from éséré, the West African name for the Calabar bean) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and the fruit of the Manchineel tree. The chemical was synthesized for the first time in 1935 by Percy Lavon Julian and Josef Pikl. It is available in the U.S. under the trade names Antilirium and Isopto Eserine, and as eserine salicylate and eserine sulfate. Today, physostigmine is most commonly used for its medicinal value. However, before its discovery by Sir Robert Christison in 1846, it was much more prevalent as an ordeal poison. The positive medical applications of the drug were first suggested in the gold medal-winning final thesis of Thomas Richard Fraser at the University of Edinburgh in 1862. Medical uses Physostigmine is used to treat glaucoma and delayed gastric emptying. Because it enhances the transmission of acetylcholine signals in the brain and can cross the blood–brain barrier, physostigmine salicylate is used to treat anticholinergic poisoning (that is, poisoning by substances that interfere with the transmission of acetylcholine signaling, such as atropine, scopolamine, and other anticholinergic drug overdoses). It is also used to reverse neuromuscular blocking. Physostigmine is the antidote of choice for Datura stramonium poisoning. It is also an antidote for Atropa belladonna poisoning, the same as for atropine. It has also been used as an antidote for poisoning with GHB, but is poorly effective and often causes additional toxicity, so is not a recommended treatment. It can also be used as an antidote for dimenhydrinate poisoning. It has been shown to improve long-term memory, and was once explored as a therapy for Alzheimer's disease, but in clinical trials it was not shown to confer convincing benefits, and it led to very common moderate to severe side-effects such as nausea, vomiting, diarrhea, loss of appetite, abdominal pain, and tremors, resulting in a high rate of withdrawal. Physostigmine's poor tolerability led to it being abandoned in favor of later acetylcholinesterase inhibitors, three of which are currently in use: donepezil, galantamine, and rivastigmine. Recently, it has begun to be used in the treatment of orthostatic hypotension. Recently, physostigmine has been proposed as an antidote for intoxication with gamma hydroxybutyrate (GHB, a potent sedative-hypnotic agent that can cause loss of consciousness, loss of muscle control, and death). Physostigmine may counteract GHB by producing a nonspecific state of