It is a reversible inhibitor of acetylcholinesterase, the enzyme responsible for the breakdown of acetylcholine in the synaptic cleft of the neuromuscular junction. It indirectly stimulates both nicotinic and muscarinic acetylcholine receptors. Physostigmine has an LD50 of 3 mg/kg in mice. Bioactivity
Physostigmine functions as an acetylcholinesterase inhibitor. Its mechanism is to prevent the hydrolysis of acetylcholine by acetylcholinesterase at the transmitted sites of acetylcholine. This inhibition enhances the effect of acetylcholine, making it useful for the treatment of cholinergic disorders and myasthenia gravis. More recently, physostigmine has been used to improve the memory of Alzheimers patients due to its potent anticholinesterase activity. However, its drug form, physostigmine salicylate, has poor bioavailability. Physostigmine also has a miotic function, causing pupillary constriction. It is useful in treating mydriasis. Physostigmine also increases outflow of the aqueous humor in the eye, making it useful in the treatment of glaucoma. Side effects
An overdose can cause cholinergic syndrome. Other side effects may include nausea, vomiting, diarrhea, anorexia, dizziness, headache, stomach pain, sweating, dyspepsia, and seizures. The carbamate functional group readily hydrolyses in water, and in bodily conditions. The metabolite thus formed from physostigmine and some other alkaloids (e.g. cymserine) is eseroline, which research has suggested may be neurotoxic to humans. Death can occur rapidly following overdose as a result of respiratory arrest and paralysis of the heart. Synthesis
Physostigmine has two stereocenters—the two carbons where the five-membered rings join—so any attempt at the total synthesis must pay attention to obtaining the correct stereoisomer.
Lentiginosis refers to the presence of lentigines in large numbers or in a distinctive configuration. These are spotted areas created by accumulation in the skin due to sun exposure. Due to a high irregularity any distinction from randomness defines lentiginosis. Although lentigines are benign, they be the signal of an underlying problem such as progressive cardiomyopathic lentiginosis, which can cause retardation in children. See also
Lentigines
Skin cancer
List of cutaneous conditions

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