moderate increase in dose often produces disorientation and con-
fusion. This may be accompanied by intense hallucinatory activity
—powerful hallucinations in which the intoxicated person loses
all capacity to distinguish between what is “real” and what is being
hallucinated. Lack of memory (amnesia) is common. The connection
between the known neurochemical action of atropine in the brain—
antagonist at mAChRs—and these powerful psychoactive effects is
completely unknown.
Now take a look at these two molecular structures:
sy H )-
Fm aAtropine
IpratropiumAtropine, as mentioned, crosses the blood-brain barrier, allowing it to
trigger powerful psychoactive effects. Ipratropium is nearly identical
except for a small, but very significant, addition to the molecule. Do
you notice what it is?
There is an additional group of atoms attached to the nitrogen—
a three-carbon isopropyl group. Attachment of a fourth structure to
the nitrogen atom produces a charged quaternary amine. The positive
charge collects water molecules around it, turning what was once
a largely hydrophobic molecule (atropine) into a hydrophilic one
(ipratropium). As a result, ipratropium does not cross the blood-brain
barrier. This allows it to be used medically as a parasympatholytic (for