Atropine synthetic substitutes

Homatropine (239a) or mandelyltropeine, a common synthetic substitute for atropine, can be distinguished from the natural product by its failure to give a positive Vitali test (1). 

Intellectual, Synthetic Substitutes of Atropine. Atropine was used for many decades as a mydriatic in ophthalmologic diagnostics. The disadvantage of the alkaloid was the enduring irritation of the patients for hours (dilated pupils). Nowadays, ophthalmologists prefer, e.g., tropicamide whose name (INN) was created in memory of its natural precursor it represents an intellectual derivative of atropine with decisive, retained structural characters of the alkaloid (Fig. 3.25). 

In addition to modifications of the morphine molecule, many purely synthetic analgesics have been produced, the first of these, pethidine (meperidine), having been synthesized in 1939 in an attempt to make a substitute for atropine (276). As in the case of heroin, pethidine was at first thought to be nonaddictive. It has been followed by a hundred or so other compounds of several different types, but, as with the morphine derivatives, none, with the possible exception of pentazocine, has been found to have analgesic without addictive properties. However, it seems that the two effects may not be entirely inseparable, as diphenoxylate, which has come into use as an antidiarrheal drug, has been found to possess the power to cause addiction but no analgesic action at all (277). 

Various drugs are invariably used in Parkinsonism for the following effects, first, to lower abnormal reflex rigidity and tremor, and restore normal motor activity e.g., natural atropine group of alkaloids, synthetic atropine substituted, antihistaminics secondly, to minimise mental depression-e.g., analeptics and thirdly, to allay restlessness, tension and anxiety-e.g., sedatives and tranquillizers. 

The pronounced pharmacological activity associated with the tropine and scopine skeletons prompted the synthesis of a number of semi-synthetic derivatives of the solanaceous alkaloids in which various other acids were substituted for tropic acid [390]. Anticholinergic activity was evident in many of these synthetic atropine-like molecules, but only two, benztropin (Cogentin, Cobrentin, 7) and ethylbenzatropin (Ponalide, 8), have found clinical use in Parkinsonism. Neither the latter nor tigloidine (9), originally isolated from... 

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