What does the numerical value of affinity (Ki) signify in pharmacology?

Affinity is expressed by the dissociation constant (Ki). The smaller the numerical value, the higher the affinity, meaning the substance is more potent and requires a lower concentration in the blood to manifest psychoactive effects.

What is the difference between an agonist and an antagonist in receptor interaction?

An agonist increases the activity of a receptor, while an antagonist (sometimes called an inhibitor) decreases or blocks the activity of the receptor.

How does aripiprazole differ from traditional antipsychotics regarding dopamine receptors?

While most antipsychotics reduce the activity of dopamine receptors, aripiprazole is unique because it increases the activity of two specific types of dopamine receptors while simultaneously modulating serotonin receptors to reduce psychotic symptoms.

Understanding psychoactive substances: receptors and affinity

Table of Contents

Affinity
The strength of affinity is given in certain numerical units. The smaller the number, the higher the affinity. Affinity is measured in the amount at which the effects of a given psychoactive substance, for example, begin to manifest. The lower the content of the substance in the blood that causes psychoactive manifestations, the greater the strength of the substance. For psychoactive substances and psychiatric and neurological drugs, it is stated which receptors the substance acts on and with what high affinity. A large number of receptors are mainly affected by antipsychotic drugs.
Furthermore, it should be noted that all receptors (e.g., dopamine and serotonin receptors) are further divided into several types of receptors.
For example, dopamine receptors are divided into D1, D2, D3, D4, and D5 receptors. GABA receptors are divided into GABA _A and GABA _B.
Serotonin receptors have an abbreviation created according to the chemical name: " 5-HT ". Serotonin receptors are divided into 5-HT1, 5-HT2, 5-HT3, 5-HT4 , etc.
The 5-HT1 receptor is further divided into 5-HT1A, 5-HT1B, 5-HT1D , etc.

Examples of the pharmacology and affinity of LSD and the antipsychotic clozapine to individual receptors
https://en.wikipedia.org/wiki/Lysergic_acid_diethylamide#Pharmacodynamics
https://en.wikipedia.org/wiki/Clozapine#Mechanism_of_action

In relation to affinity, it is also important whether the receptor is acted upon as an agonist or antagonist, i.e., whether the activity of the receptors is increased or decreased by the receptor.

Affinity is expressed in numbers, the dissociation constant (K _i ). There are no negative values, it is always stated with the affinity for a given type of receptor whether it is agonism or antagonism, i.e. it is an increase or decrease in the activity of the given receptor. Antagonism is sometimes also called inhibition.

There are several types, ways, and mechanisms by which the activity of a given receptor can be increased. For example, some substances act only on certain types of dopamine or serotonin receptors. Furthermore, the same substance can, for example, increase the activity of some types of serotonin receptors and decrease the activity of others. This is the case with some atypical antipsychotics.

A very interesting antipsychotic is, for example, aripiprazole https://en.wikipedia.org/wiki/Aripiprazole#Pharmacology . Although all antipsychotics reduce the activity of dopamine receptors, this one increases the activity of two types of dopamine receptors, and also reduces the activity of some types of serotonin receptors and increases the activity of others. And it is precisely because it reduces the activity of the types of serotonin receptors that are most responsible for psychotic symptoms that this is sufficient for the drug to have antipsychotic effects. It increases the activity of the types of serotonin receptors that are not responsible for psychotic symptoms.

Reuptake inhibition

There are psychiatric drugs that are inhibitors of the reuptake of serotonin, noradrenaline, and dopamine. Sometimes, it can be the inhibition of the reuptake of more than one neurotransmitter. Drugs such as cocaine and methamphetamine also inhibit the reuptake of dopamine, noradrenaline, and serotonin at the same time, although each substance does so in a slightly different way.

https://en.wikipedia.org/wiki/Cocaine#Pharmacology

https://en.wikipedia.org/wiki/Methamphetamine#Pharmacology

Reuptake inhibition is characterized by increasing the activity of all types of receptors bound to the neurotransmitter evenly . Other psychoactive substances mainly act only on some types of receptors of the neurotransmitter (e.g. LSD). Reuptake inhibition never reduces the activity of the given receptor.

Monoamine oxidase inhibitors (MAOIs)

MAOIs have many common features, or are very similar in their final effect to reuptake inhibitors. They also evenly increase the activity of all types of receptors of a given neurotransmitter. These are receptors bound to serotonin, dopamine and noradrenaline. Monoamine oxidase inhibitors are divided into two types: MAOI-A and MAOI-B. MAOI- A mainly increases the activity of serotonin and noradrenaline receptors and to a lesser extent increases the activity of dopamine receptors, MAOI-B mainly increases the activity of dopamine receptors and to a lesser extent increases the activity of serotonin and dopamine receptors.