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Solutions For An Introduction to Medicinal Chemistry Chapter 11 Problem 3Q

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Solution 1

Morphine has an analgesic activity on the body as a result of its binding to receptors for opioids present in the brain. In vitro studies show that a quaternary salt of morphine also has strong binding affinity for such receptors. However, unlike morphine, the quaternary salt does not have any biological activity in vivo.

The quaternary salt of morphine is inactive in vivo due to the presence of the blood brain barrier. The polarity and permanent positive charge of the salt render it unable to cross the blood-brain barrier, and thus it cannot even reach the receptors it needs to bind to in order to be biologically active.

This is different from how in vivo studies are carried out, as they do not take into account the possible obstructions within the body that can prevent the drug or salt from reaching its intended receptor. These studies do establish, however, that in the absence of the blood-brain barrier, both morphine and its quaternary salt would be biologically active.

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Solutions For Problems in Chapter 11