Activity in the human brain is governed by a multitude of complex chemical processes. The neurotransmitters constantly transmit an incalculable number of signals between the neurons, which are received through a receptor – a protein of the membrane of neural cells to which a neurotransmitter, a drug or a hormone can bind to and create a biochemical reaction in the brain.
In order for the receptor to produce a biological response in the human brain, it needs to be activated by a chemical that binds to it, thus triggering its activation. An agonist, i.e. a drug that sets off the natural response of the receptor, is responsible for prompting this action.
However, there is a special type of receptor ligand, i.e. a chemical substance or drug that becomes a part of the biomolecule and blocks the biological response of the receptor. These types of drugs are called antagonist drugs or blockers, because they inhibit, block, or reverse the action potential of the neuron receptor.
In this way, the neural path of the stimuli received through the sensory organs becomes deterred or blocked.
How Do Antagonist Drugs Work?
Most drugs work by binding to a targeted receptor in order to block or tone down its effect. At the receptor’s site, the antagonist drugs reduce the activity of the agonist by selectively interacting with the protein molecules of the cells. Put simply, when the antagonists bind to a receptor, that receptor loses the ability to receive sensory signals and information.
Some antagonist drugs have enzymes as their target, instead of receptors. By this type of bonding, they regulate the rate of chemical reactions. These types of drugs are classified as inhibitors or activators (inducers). Such are aspirin, cox-2 inhibitors, as well as HIV protease inhibitors.
How Do We Divide Antagonists According to Their Interaction With The Receptors?
Basically, there are several types of antagonists, categorized according to the way they interact with their targeted protein receptor:
- Competitive Antagonists (reversible, surmountable beta-blockers)
- Non-competitive Antagonists (irreversible, insurmountable alpha-blockers)
- Uncompetitive Antagonists
- Silent Antagonists
- Partial Antagonists
- Full Antagonists
- Inverse Antagonists
Competitive Antagonists (reversible, surmountable beta-blockers)
As their name implies, these antagonists ‘compete’ with the agonist drugs by binding to the same receptor. However, unlike the agonists, the antagonists do not activate the receptor of the targeted cell.
A large concentration of antagonist drugs at a particular receptor blocks the agonists from occupying and activating it. This is used in case there is a need to prevent or reverse the effect of some drugs that have previously been taken by an individual.
Their surmountable quality means that the reversible antagonists will eventually free the receptor, thus making it available to be occupied and activated by the agonists.
Beta-blockers are drugs that temporarily block or reduce the effect of the adrenaline hormone, mainly for reducing blood pressure and heart rate. Consequently, they are prescribed for medical conditions such as high blood pressure, arrhythmia of the heart, angina, anxiety, migraine, etc.
The list of competitive antagonist drugs and beta-blockers includes:
- Atropine
- Naloxone
- Ketamine
- Acebutolol (Sectral)
- Atenolol (Tenormin)
- Bisoprolol (Zebeta)
- Metoprolol (Lopressor, Toprol XL)
- Nadolol (Corgard)
- Nebivolol (Bystolic)
- Propranolol (Inderal, InnoPran XL)
Non-competitive Antagonists (Irreversible, Insurmountable Alpha-Blockers)
Unlike the binding of the reversible antagonists, the bond that non-competitive irreversible antagonists make with the receptors is unbreakable and permanent. Their effect cannot be influenced by any amount of agonist drugs.
On the other hand, the insurmountable quality of the bond these antagonists create to reduce the maximum effect of the agonists cannot affect the inhibition caused by the antagonist drugs even in the highest concentrations.
Alpha-blockers block the hormone norepinephrine, relaxing the walls of the smaller arteries and veins in order to support blood flow and lower blood pressure.
The list of non-competitive antagonist drugs and alpha-blockers includes:
- Losartan
- Alfuzosin (Uroxatral)
- Doxazosin (Cardura)
- Prazosin (Minipress)
- Silodosin (Rapaflo)
- Tamsulosin (Flomax)
- Terazosin (Hytrin)
Uncompetitive Antagonists
Unlike the non-competitive antagonists, the uncompetitive antagonist drugs need a receptor that has previously been activated by an agonist in order to bind with it.
The list of uncompetitive antagonist drugs includes Memantine. It reduces the action of chemicals in the brain.
Silent Antagonists
These antagonists are, in fact, the true antagonists. Namely, they are labeled as ‘silent’ because they possess zero potential for activation of the receptors. They bind only to ligand-depended receptors.
Partial Antagonists
This type of antagonist drug possesses both agonist and antagonist characteristics. It can act as an antagonist in the presence of an agonist at the target site of the receptor, but can not reach the full potential.
Due to these characteristics, the partial antagonists can also be considered as ligands. Namely, while blocking the excessive activity of the receptors, they also stimulate the deficient tissues of the neuron cell.
The list of partial antagonist drugs includes:
- Buprenorphine
- Butorphanol
- Pentazocine
- Tramadol
Full Antagonists
The full antagonist drugs have the ability to bind to a target receptor and activate its full potential.
The list of full antagonist drugs includes:
- Codeine
- Fentanyl
- Heroin
- Hydrocodone
- Methadone
- Morphine
- Oxymorphone
Inverse Antagonists
The inverse antagonist drugs not only block the action of the agonist by binding at the same place, but they also produce an opposite action by decreasing the activity.
The list of inverse antagonist drugs includes:
- Naloxone
- Naltrexone
- Melanocortin
- All antihistaminic drugs
What Are the Types of Antagonist Drugs According to the Mechanism They Use?
Depending on the mechanism used for triggering a biological response, we can distinguish the following antagonists:
- Chemical Antagonists
- Pharmacological Antagonists
- Physical Antagonists
-
Allosteric Antagonists
- Inverse Antagonists
Chemical Antagonists
When the drug causes an effect that blocks the formation of another chemical molecule, it has the properties of a chemical antagonist.
Pharmacological Antagonists
This type of antagonist drug binds at the same receptor spot as the agonist drug, thus blocking its access to the targeted receptor and preventing its activation.
Physical Antagonists
The physical properties of the drug motivate the actions of this type of antagonist. Namely, when medicine charcoal is used to prevent poisoning, the molecules of the charcoal act as physical antagonists by binding to the molecules of the agonist drug in order to block its effect.
Allosteric Antagonists
The allosteric antagonists bind to a different receptor of the agonist drug. They can both change the binding site in a way it becomes no longer available for the agonist drugs, and also continue blocking the activation of the receptor after an agonist binds to it.
Inverse Agonists
The inverse agonists perform the same functional characteristics as antagonist drugs.
Which Antagonists Are Most Important for the Central Nervous System?
Some antagonists are of greater importance for the central nervous system. These include the following:
- Dopamine Antagonist (D1 and D2 blockers)
- Serotonin Antagonists
Dopamine Antagonist Drugs
By blocking the dopamine receptors, these antagonist drugs are used in therapy for several medical conditions and diseases, such as schizophrenia, bipolar disorder, stimulant psychosis, nausea, and vomiting.
The list of dopamine antagonist drugs includes:
- Metoclopramide (Reglan)
- Prochlorperazine (Compazine)
- Droperidol (Inapsine)
- Promethazine (Phenergan)
- Haloperidol
- Chlorpromazine
- Fluphenazine
Serotonin Antagonist Drugs
As their name implies, these antagonist drugs inhibit the activation of the serotonin receptors. They have been implemented in the therapy administered to patients suffering from psychiatric diseases, such as anxiety, insomnia, depression, etc.
The list of serotonin antagonist drugs includes:
- Dolasetron
- Granisetron
- Ondansetron
- Palonosetron
- Tropisetron
What Makes Us Happier – Serotonin or Dopamine?
Both serotonin and dopamine are neurotransmitters, i.e. hormones. They regulate similar processes which aid the bodily functions, yet have different effects.
While serotonin regulates our satisfaction, happiness, and optimism, dopamine is in charge of our mood, the regulation of the control and reward systems in the brain, as well as muscle movement. However, they both have a role in sleep, the formation of memory, as well as the regulation of metabolic processes and emotions.
What Is Dopamine?
Dopamine is a hormone – a neurotransmitter that is released in the brain. It supports the brain processes that control and regulate motivation, desire, as well as cravings.
The levels of dopamine influence the following bodily functions:
- Mood
- Sleep cycles
- Cognitive processes (especially learning)
- Muscle movement
- Alertness and concentration
- Blood flow
High levels of dopamine in the blood can result in euphoric feelings, increased concentration, and motivation.
What Is Serotonin?
Just like dopamine, serotonin is a neurotransmitter hormone responsible for the transmission of information among the neurons of the brain.
The levels of serotonin influence the following functions of the body:
- the sleep-wake cycle
- mood and emotions
- metabolism and appetite
- cognition and concentration
- hormonal activity
- body temperature
- appetite
Unlike dopamine, which is stored in the brain, serotonin is stored mainly in the digestive system of the human body. Hence, low serotonin levels in the body can lead to low energy, sadness, moodiness, sugar craving, irritability, etc.
On the other hand, the increased levels of serotonin in the bloodstream of the body can lead to feelings of happiness, but can also regulate our appetite and metabolism.
Interaction Between Dopamine and Serotonin
Even though similar in function, these two neurotransmitters have opposite effects on some of our bodily functions. In some cases, serotonin blocks the production of dopamine, which can lead to impulsive behavior.
Also, while serotonin suppresses appetite, dopamine increases it by stimulating our feeling of hunger in the brain.
To Sum Up
Antagonist drugs have been created in order to directly block, inhibit, or oppose the influence of the activity of agonists. The antagonists bind themselves to a targeted receptor of the cell and produce a response from the cell. By taking over their place at the receptor’s site, they reverse the effects of the agonists and prevent them from accessing the receptors.
The antagonist drugs can be categorized according to the mechanisms they use for triggering a biological response and the types of interaction they have with the receptors.
Dopamine and serotonin are the most important neurotransmitters included in the antagonistic processes of the central nervous system. While the later neurotransmitter is labeled as the happiness molecule (hormone), the former is called the motivation molecule (hormone).
Fun Facts
Did you know?
- Behind every thought, action, or dream there is a complex chemical process developed and conducted in our brain.
- Beta-blocker antagonists drugs are prescribed in cases when our heart rate needs to be lowered.
- The side-effects of beta-blockers include weight gain, dizziness, fatigue, and a feeling of coldness in our hands and feet.
- The uncompetitive antagonist Memantine reduces compulsive eating behavior, i.e. it regulates the uncontrollable consumption of food.
- Alcohol activates and stimulates the activity of the serotonin, dopamine, and endorphins hormones. In this way, it becomes their agonist.
- All addictive substances or drugs act as agonists. They include nicotine, alcohol, heroin, methadone, opium, etc.
- Since the antagonists can stop the effect of the agonists, they are used as therapy in drug addiction treatments.
- Dopamine antagonists are also labeled as antipsychotic drugs, used in the treatment of hallucinations, delusions, mania, schizophrenia, bipolar disorder, and severe psychosis.
- Serotonin and dopamine are the so-called happiness and motivation hormones, respectively. Their levels increase significantly during physical training, such as aerobics and sports, as these activities lower the levels of cortisol, i.e. the stress hormone. Actually, apart from learning, physical exercising is the best thing we can do for both our brain and our body.
- However, too much exercise can create the opposite effect. Namely, prolonged physical effort can be perceived by the brain as a form of negative stress. In such a case, the cortisol levels rise and increase anxiety and fatigue instead of the level of happiness.