Structural Biochemistry/Drug Antagonists

Definition

An example of receptors. This is the Mu Opioid receptor.

Drug antagonists are designed to bind to receptors and specifically block or weaken drug effects. The antagonist itself does not have any biological effects. In general, drug antagonists are used by doctors to help patients through withdrawal or patients who overdose. By taking an antagonist, the receptors for the specific drug is blocked and therefore weakened or completely shut down. The effectiveness depends on the nature of the binding receptor.

Chemistry

A ligand can bind to biochemical receptors that in turn becomes activated. In the case of drugs, the drugs act as the ligand. Receptors can be both intracellular and extracellular. They can exist in the nucleus and mitochondria or even the membrane. A ligand can cause effects by binding to either the receptor itself (active site), or to allosteric receptors. Allosteric sites are other sites on the receptor that are not classified as an active site. Both regular the activity of the receptors. Antagonists help block these interactions and prevent agonist-induced responses. When agonists bind to the receptor, they turn 'on' the cellular responses. When antagonists bind to receptors, they turn 'off' cellular responses. Often, the efficiency of antagonists depend on where the drug is designed to attach on the receptor. However, in all cases, an antagonist is defined as having no biological effects of its own. Because of this factor, it is useful in drug and withdrawal treatment in humans.

Classifications of Drug Antagonists

Competitive- These antagonists bind at the same site that the target ligand or agonist binds to. However, it does not activate the receptor sites, but rather blocks it so that the target ligand or agonist cannot attach and activate the site.

Non-competitive- These antagonists bind to allosteric sites and is effective from there. It does not need to attach to the same site as the target ligand or agonist to block or dampen its effects.

Uncompetitive- Uncompetitive antagonists cannot work on their own. Instead they require the ligand or agonist to be bound to the receptor site before they can attach themselves to an allosteric site and begin their work. In general, these antagonists block higher concentrations of agonists better than lower concentrations.

Partial Antagonist- Partial antagonists can attach to the active site but do not completely block out the receptor's effects. However, it does lower it from its maximum potential.

Silent Agonists- These antagonists have zero ability to activate a receptor. They simply attach and block the receptor from activating.

Inverse Agonists- They attach to the same site as an agonist, but induce biological responses opposite to that agonist.

Examples of Drug Antagonists

Naloxone.

Naloxone- Is a drug antagonist that blocks the effects of opiates. It is administered via injection. In many cases, naloxone is used to counter overdose of opiates such as a heroin overdose. It is made from thebain. It is a μ-opioid receptor and has rapid blockage of withdrawal symptoms which are especially dangerous in patients who have overdosed. Naloxone is also used in conjunction with other drugs to prevent drug abuse. For example, amounts of naloxone is present in suboxone. Subonxone is used to help detoxify patients by administering lower and lower amounts of opiates over time. However it can also be addictive. Therefore, naloxone is used to partially block out the opiate effects in Subonxone.

Naltrexone- It is also an opiate antagonist. Additionally, it can be used effectively as an alcohol dependence manager. However, Naltrexone is orally administered and is classified as a competitive antagonist. Compared to Naloxone, it is longer acting and irreversibly. Therefore, it serves better as an emergency antidote rather than the primary antidote. This antagonist is active at μ- and κ-opioid receptors. Recent studies have shown that low doses of Naltrexone may be able to treat for Cronh's disease. Further studies are planned.

Buprenorphine- Buprenorphine is a partial opiate antagonist. It binds at the µ- and κ-opioid receptor. Buprenorphine is a thebaine derivative that is a partial agonist at the u and k receptor points. It helps block and weaken opiate effects. It binds very tightly to the receptors in the brain, making it hard for opioids to take effect when it is inside the body.

References

1. Hart, Carl. Drugs, Society, and Human Behavior. 13th. McGraw-Hill Humanities, 2008. Print.

2. http://en.wikipedia.org/wiki/Receptor_antagonist

3. Berg, Jeremy; Tymoczko, John; Stryer, Lubert. Biochemistry, 6th edition. W.H. Freeman and Company. 2007