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Both Scopolamine and Atropine are muscarinic antagonists, having essentially the same action: blocking parasympathetic nerve receptors.

The action on the brain by muscarinic antagonists is presumed to be caused by dilation of blood vessels, thus we might expect the effect on the brain by the two compounds to be similar.

However, in actuality the action of the two compounds on the brain is somewhat different. Scopolamine begins causing strong psychotropic effects even in very small doses before it has any effects on the skeletal nervous system. Conversely, atropine begins having effects on the muscular system long before it begins having psychotropic effects and in fact, potentially toxic doses of atropine have to be administered before significant psychotropic effects begin manifesting.

If the apparent biochemical action of the two compounds is similar, why do we see this difference in the effects between the two with regards to the brain?

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It seems that the reason for the different effect of Atropine and Scopolamine on the brain is related to the structural difference between them. From the chemical structures below it is evident that the two molecules are almost identical, save for an epoxide group that is found in Scopolamine but not in Atropine.

Atropine and Scopolamine chemical structures

According to Brody's Human Pharmacology: Molecular to Clinical, 5th edition, 2010, pp. 113-115, this epoxide reduces Scopolamine's base strength and enables it to penetrate into the brain more readily than Atropine. Faster penetration into the brain = earlier appearance of psychotropic effects.

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