Physostigmine pharmacological action

The miotic effect induced by physostigmine lends itself to investigation of the interrelation of chemical constitution and pharmacological action, and Stedman has devoted much attention to this subject. Eseroline is devoid of miotic activity, so that the latter action in physostigmine must be mainly due to the fact that it is a methylurethane, and, since activity only becomes evident in the urethanes of phenolic bases or phenols with a basic side-chain, a basic nucleus for the urethanes appears also to be essential. 

The pharmacological actions of physostigmine are similar to those of cholinergic drugs. Topical instillation into the eye produces miosis, spasm of accommodation and decrease in intraocular pressure. Physostigmine is well absorbed after oral as well as parenteral administration and also produces central cholinergic actions because of penetration into blood brain barrier. 

Reversible cholinesterase inhibitors form a transition state complex with the enzyme, just as acetylcholine does. These compounds are in competition with acetylcholine in binding with the active sites of the enzyme. The chemical stracture of classic, reversible inhibitors physostigmine and neostigmine shows their similarity to acetylcholine. Edrophonium is also a reversible inhibitor. These compounds have a high affinity with the enzyme, and their inhibitory action is reversible. These inhibitors differ from acetylcholine in that they are not easily broken down by enzymes. Enzymes are reactivated much slower than it takes for subsequent hydrolysis of acetylcholine to happen. Therefore, the pharmacological effect caused by these compounds is reversible. 

Physostigmine reversibly inhibits the action of the enzyme acetylcholinesterase thereby increasing the level of acetylcholine in the synaptic cleft of the neuromuscular jimction thereby counteracting the agent s pharmacological effects. 

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