Prodrugs and Chemical Delivery Systems

A drug that is inactive when administered but is converted into an active form within the body.

The amino acid precursor of dopamine, used as a treatment for Parkinson's disease.

A specialized transport system that selectively carries L-amino acids into the central nervous system.

The conversion of inactive L-dopa into the active neurotransmitter dopamine.

The drug that activates the brain's active transport system to carry L-dopa into the brain.

The inability of dopamine to readily cross the blood-brain barrier.

The rapid breakdown of dopamine by enzymes in the body.

The undesirable effects of a drug on tissues and organs outside of the intended target.

The ability of L-dopa to reach the brain while encountering side effects in other tissues.

The prodrug form of 2-PAM, an antidote for insecticide and nerve agent poisoning.

Pro-2-PAM is a drug that is inactive until it is oxidized into its active form, 2-PAM. This process of oxidation traps the active drug within the brain.

Pro-2-PAM is a non-ionic compound. This means it doesn't carry an electrical charge. Non-ionic compounds can easily pass through the blood-brain barrier.

When pro-2-PAM is oxidized to 2-PAM, it becomes a positively charged ion. Positively charged ions cannot easily cross the blood-brain barrier, effectively trapping the active 2-PAM within the brain.

The oxidation of pro-2-PAM occurs in both the brain and the rest of the body, generating similar levels of 2-PAM in both places.

Administering pro-2-PAM directly into the bloodstream (IV) results in brain levels of 2-PAM that are 10 times higher than if you administered 2-PAM directly into the bloodstream.

Dihydropyridine derivatives are used to deliver a variety of drugs to the central nervous system (CNS) by exploiting their ability to cross the blood-brain barrier and undergo oxidation.

This method of drug delivery involves three main steps: 1) The drug-dihydropyridine derivative crosses the blood-brain barrier, 2) It undergoes oxidation to become trapped in the brain, 3) The drug is released from the trapped form through a second metabolic event.

Different functional groups can be added to the dihydropyridine molecule to create derivatives compatible with various drugs used in the CNS.

Many CNS drugs are amines, which can be degraded in the body before reaching their target. Amines can be attached to dihydropyridine carboxylic acids to form amides, protecting them from degradation during transport to the brain.

This example shows L-dopa, a dopamine precursor, attached to a dihydropyridine molecule. This derivative can cross the blood-brain barrier. Once trapped, the derivative undergoes hydrolysis to release the active L-dopa.

The delivery of drugs directly to the colon and lower GI tract, utilizing the enzymatic processes of colon bacteria. These bacteria have glucosidase activity, which breaks down glucoside derivatives of drugs, leading to higher concentrations of the active drug in the colon.

Glucoside derivatives of certain steroids are absorbed poorly in the GI tract, remaining available for processing by colon bacteria. This strategy ensures higher drug concentration in the lower GI tract.

Tumor cells often exhibit increased enzymatic activity compared to normal cells, linked to their faster growth rates. This difference in activity is targeted for drug delivery.

Peptidases and proteolytic enzymes are among the enzymes found in higher concentrations within and around tumor cells. These enzymes can be used to target drug delivery to tumors.

A strategy for targeting drugs to tumors uses the fact that tumor cells have a higher concentration of certain enzymes. This involves modifying drug molecules with amino acids or peptides, which are then broken down by these enzymes, releasing the active drug near the tumor.

While enzymes are more concentrated in tumor cells, their presence in normal cells prevents complete site-specificity. This means that the drug may have some activity in normal tissue as well.

Glucosidase activity is a characteristic of bacteria in the colon, and it helps break down glucoside derivatives of drugs, producing higher concentrations of active drug in the colon.

The enzyme activity in tumor cells offers a potential advantage for drug delivery. The higher activity of certain enzymes in tumor cells can be exploited to concentrate the drug at the tumor site.

Drug delivery to tumors often utilizes the fact that tumor cells have a higher concentration of certain enzymes. This allows for a more targeted drug delivery, potentially improving treatment effectiveness.

Glucoside derivatives of steroids are not well absorbed in the upper GI tract, which allows them to reach the colon, where they are broken down by colon bacteria. This leads to a higher concentration of the active drug in the colon, potentially improving its effectiveness.