Physostigmine practicability

I can almost hear some of the musings of the unbelievers After all, this study was done by psychiatrists. Who knows, maybe they absent-mindedly moved the decimal points. In any case, the new treatment method did not make it into mainstream American psychiatry, much less general medical practice. Nor did the good news that physostigmine was an effective antidote for atropine delirium. (Incidentally, I met Forrer s colleague. Dr. Miller, in 1981, 30 years after their first publications about atropine coma therapy. He was invited to... 

Organocatalytic asymmetric alkylation methodology has also been efficiently applied in a practical multi-gram synthesis of pharmaceutically interesting, optically active (—)-physostigmine analogs [7]. In the presence of 15 mol% of the catalyst 13 alkylation of the oxindole substrate 12 with chloroacetonitrile furnished the desired product 14 in 83% yield and 73% ee (Scheme 3.3, Eq. 2). The counter-ion of the... 

The cholinesterase inhibitors have multiple practical applications - from medicine to warfare. Physostigmine was actually the first practically used cholinesterase antagonist. To describe its initial use as medical , however, would mean a bit of a stretch - instead, the seed containing it was used to extort confessions from persons accused of crimes or witchcraft in Guinea. This seed used to be called the ordeal bean by the local people. 

This lactonization was later extended to indole derivatives [123], and the influence of different groups on sulfur on the process was explored within an application to the total synthesis of the alkaloid physostigmine [124] (Scheme 14). Thus methyl indolyl sulfoxides rendered practically racemic... 

This method, however, is still not practical from a synthetic point of view, because a much more efficient synthesis of 29 and an equivalent oxindole 12 of the Jones synthesis had already been established in 1935 by Julian and Pikl starting from p-ethoxyacetanilide (131) and employing the intramolecular Friedel-Crafts reaction in the synthesis of physostigmine (1) 38,44) (Scheme 20). 

Once again, this useful finding apparently received little attention from mainstream clinicians. The fact that physostigmine had been largely replaced in clinical practice by neostigmine and pyridostigmine, neither of which has much central antimuscarinic activity, may account for this curious oversight. 

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