Clera Antipsychotic Science

Summary

The script reveals a surprising discovery in neuroscience: all antipsychotic medications target a specific region in the brain, the caudate putamen, which is rich in dopamine type 2 receptors. These receptors are crucial for motor control and are also linked to psychological functions. The script delves into the molecular interaction between dopamine and antipsychotics like haloperidol and olanzapine, highlighting how they block dopamine receptors, leading to varying degrees of efficacy and side effects, including Parkinsonism and tardive dyskinesia.

Takeaways

• 🧠 The discovery of a common target in the brain for all antipsychotics was a significant revelation, contrary to the belief that they acted in various parts of the brain.
• 💊 Antipsychotic medications primarily target the type 2 dopamine receptor, which is abundant in the caudate putamen region of the basal ganglia, responsible for motor control.
• 🤔 Dopamine type 2 receptors are also found in areas associated with psychological functions, such as the cingulate gyrus, cerebral cortex, and nucleus accumbens.
• 🔍 At the molecular level, dopamine is released in pulses and binds to its receptors rapidly, with antipsychotics like haloperidol blocking this access and affecting dopamine transmission.
• 🆚 There is a competitive interaction between dopamine and antipsychotic drugs for receptor binding, with tightly bound drugs like haloperidol winning the competition.
• 💊 Haloperidol is a long-acting drug, with a dose of 10 milligrams lasting for days, which is beneficial for controlling psychotic symptoms but can lead to accumulation and side effects over time.
• 🚫 High blockade by haloperidol can cause extrapyramidal symptoms, such as Parkinsonism, elevated prolactin levels, amenorrhea, and tardive dyskinesia.
• 💊 Olanzapine is another antipsychotic effective at lower doses but can produce Parkinsonism and a risk of tardive dyskinesia at higher doses.
• 📈 The risk of weight gain is associated with olanzapine use, which is an important consideration when prescribing this medication.
• 🔄 The script emphasizes the importance of understanding the molecular interactions of antipsychotics with the brain's dopamine system to manage their therapeutic effects and side effects effectively.

Q & A

What was the surprising discovery about the common target of antipsychotics in the brain?

The surprising discovery was that all antipsychotics have a common target in the brain, which is the Spartan in the brain. This was unexpected as it was previously believed that antipsychotics acted on many parts of the brain and various proteins and receptors.

How many types of dopamine receptors are there in the brain, and which one is targeted by antipsychotic medication?

There are five types of dopamine receptors in the brain. Antipsychotic medication specifically targets the type 2 receptor.

In which part of the brain are the type 2 dopamine receptors predominantly located, and what is its primary function?

Type 2 dopamine receptors are predominantly located in the caudate putamen in the basal ganglia of the brain, which is primarily responsible for motor control of the body, including the arms and legs.

Which brain regions are associated with psychological functions and also contain type 2 dopamine receptors?

The cingulate gyrus, the cerebral cortex, and the nucleus accumbens are brain regions associated with psychological functions that also contain type 2 dopamine receptors.

What happens at the molecular level when dopamine is released by nerve cells?

Dopamine is released by nerve cells at a rate of five times per second in great pulses. The molecule then travels to the receptor area, which is just 100 angstroms away, and binds to the receptor very quickly, potentially a million times a second.

How does haloperidol, an antipsychotic, affect the interaction between dopamine and its receptors?

Haloperidol blocks access to the receptor by dopamine, creating a competition between the drug and the dopamine molecule. In this competition, haloperidol, being tightly bound, usually wins, resulting in partial blocking of dopamine transmission.

What is the difference in the way olanzapine blocks the dopamine receptor compared to haloperidol?

While olanzapine also blocks the dopamine receptor, dopamine molecules can still out-compete some of the olanzapine, allowing for some modest transmission of dopamine.

How does the dosing of haloperidol affect its binding to the receptor and its duration in the body?

Haloperidol is a tightly bound drug that comes off slowly. A dose of 10 milligrams per patient per day can stay in the body for a day or two or more, which is beneficial for controlling psychotic symptoms.

What are the potential long-term effects of continuous daily dosing of haloperidol?

Continuous daily dosing of haloperidol can lead to an accumulation of the drug, causing tardive dyskinesia and extrapyramidal symptoms.

At what level of blockade by haloperidol does parkinsonism become a risk?

Parkinsonism becomes a risk when there is more than 80% blockade by haloperidol.

What are some side effects associated with olanzapine use?

Olanzapine can cause parkinsonism at doses above 20 or 30 milligrams per day, and there is a risk of tardive dyskinesia and weight gain.

Outlines

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🧠 Dopamine Receptors and Antipsychotic Action

The script discusses the surprising discovery that all antipsychotic medications target a common brain region, the caudate putamen in the basal ganglia, which is rich in dopamine type 2 receptors. These receptors are crucial for motor control and are also found in areas associated with thinking and feeling. The script explains the molecular interaction between dopamine and antipsychotics, such as haloperidol and olanzapine, which block dopamine receptors, leading to a reduction in psychotic symptoms. However, long-term use can result in side effects like tardive dyskinesia and parkinsonism due to the high blockade of dopamine receptors.

Keywords

💡Spartan

In the context of the script, 'Spartan' refers to a single region in the brain that is the common target of all antipsychotic medications. This is significant because it contrasts with the previously held belief that antipsychotics acted on multiple parts of the brain. The term 'Spartan' is used metaphorically to denote a singular, central focus amidst a variety of targets.

💡Antipsychotics

Antipsychotics are a class of psychiatric medication primarily used to treat psychotic disorders such as schizophrenia. The script reveals a surprising discovery that all antipsychotics target a common brain region, highlighting the complexity and specificity of these drugs in managing mental health conditions.

💡Dopamine receptors

Dopamine receptors are proteins found in the brain that respond to the neurotransmitter dopamine. The script specifies that there are five types, but antipsychotic medications target the type 2 receptor, which is crucial for their therapeutic effects on mental health.

💡Caudate putamen

The caudate putamen is a region in the basal ganglia of the brain involved in motor control. The script mentions that type 2 dopamine receptors are abundant in this area, which is relevant to the side effects of antipsychotics on movement.

💡Basal ganglia

The basal ganglia are a group of structures deep in the brain that are involved in a variety of functions, including motor control and learning. The script discusses the concentration of type 2 dopamine receptors in the caudate nucleus and putamen, which are parts of the basal ganglia.

💡Cingulate gyrus

The cingulate gyrus is a part of the brain involved in various cognitive and emotional processes. The script indicates that dopamine type 2 receptors located here are presumably associated with thinking and feeling, which is significant for understanding the psychological effects of antipsychotics.

💡Cerebral cortex

The cerebral cortex is the outer layer of the brain responsible for higher cognitive functions such as thought and consciousness. The script mentions the presence of dopamine type 2 receptors in the cerebral cortex, linking them to the psychological effects of antipsychotic drugs.

💡Nucleus accumbens

The nucleus accumbens is a region of the brain involved in reward, pleasure, and addiction. The script's mention of dopamine type 2 receptors in this area is relevant to the understanding of how antipsychotics may influence these processes.

💡Haloperidol

Haloperidol is a specific antipsychotic drug mentioned in the script. It is described as a tightly bound drug to the dopamine receptor, effectively blocking dopamine transmission and thus managing psychotic symptoms, but also potentially causing side effects like tardive dyskinesia.

💡Olanzapine

Olanzapine is another antipsychotic medication discussed in the script. It is noted for its effectiveness at lower doses and its potential to cause side effects such as parkinsonism and weight gain at higher doses, as well as the risk of tardive dyskinesia.

💡Tardive dyskinesia

Tardive dyskinesia is a serious side effect of antipsychotic medications characterized by involuntary movements. The script explains that long-term use of certain antipsychotics, like haloperidol, can lead to this condition due to the accumulation of the drug in the brain.

Highlights

The discovery that all antipsychotics target a common region in the brain, the caudate putamen in the basal ganglia, was a big shock.

Antipsychotics were previously thought to act on many parts of the brain, but this finding identified a single common target.

There are five types of dopamine receptors in the brain, but only the type 2 receptor is targeted by antipsychotic medication.

Type 2 dopamine receptors are abundant in the caudate nucleus and putamen, which are primarily involved in motor control.

Psychologically relevant dopamine type 2 receptors are also found in the cingulate gyrus, cerebral cortex, and nucleus accumbens, which are associated with thinking and feeling.

At the molecular level, dopamine is released in pulses 5 times per second and binds to receptors very quickly, potentially a million times per second.

Antipsychotics like haloperidol block dopamine's access to the receptor, creating a competition between the drug and the neurotransmitter.

Haloperidol is tightly bound and wins the competition with dopamine, partially blocking dopamine transmission.

Olanzapine also blocks the dopamine receptor, but dopamine molecules can still out-compete some of the olanzapine, allowing for some transmission.

Haloperidol has a long duration of action, with a dose of 10 milligrams lasting for days, which is beneficial for controlling psychotic symptoms.

However, long-term daily dosing of haloperidol can lead to the accumulation of the drug and cause tardive dyskinesia and extrapyramidal symptoms.

Tardive dyskinesia and extrapyramidal symptoms can occur when there is more than 80% blockade by haloperidol.

Olanzapine is effective at doses of 10-20 milligrams per day and can cause parkinsonism at higher doses.

There is a risk of tardive dyskinesia with olanzapine at doses above 20-30 milligrams per day.

Olanzapine can also cause weight gain as a side effect.

Transcripts

the idea that I could find one Spartan

in the brain which was the common target

of all antipsychotics came as a big

shock to everyone I was told that

antipsychotics acted in many many parts

of the brain many many proteins many

receptors and here I found one region

which was common to all the a different

antipsychotic there are five types of

dopamine receptors in the brain but the

one that is the target for

anti-psychotic medication is the type 2

receptor and the type 2 receptors are

very rich in the caudate putamen in the

basal ganglia of the brain the caudate

nucleus and the putamen and that has

primarily motor control of the body arms

and legs and then there are

psychologically located dopamine type 2

receptors found in the cingulate gyrus

and the cerebral cortex nucleus

accumbens all these mysterious parts of

the brain presumably associated with

thinking and feeling imagine if we could

shrink down to the size of a molecule of

dopamine or one of these first-line

antipsychotic agents what would we see

down there at the molecular level as the

dopamine is released by the dopamine

nerve cells at five times per second in

great pulses the dopamine molecule then

arrives at the receptor area just 100

angstroms away and it goes on and off

the receptor very very quickly perhaps

as many as a million times a second and

in the presence of an anti-psychotic

like halo peridot the access to the

receptor by dopamine is blocked so there

is a competition between halo paradol

and dopamine and in this case halo

paradol being tightly bound wins the

competition and dopamine transmission is

partly blocked

olanzapine also blocks the dopamine

receptor but the dopamine molecules are

still able to out-compete some of the

olanzapine so that there's some modest

transmission he'll a pair at all is a

tightly bound drug it comes off slowly

but it's dose at 10 milligrams per

patient per day stays on for a day or

two or three or more and that's good

news to control the psychotic

symptomatic G but over the years if that

dosing continues daily and weekly and

monthly then that accumulates and causes

tardive dyskinesia extrapyramidal

symptoms kick in when there's more than

80% blockade by halo peridot so that

it's relatively easy with halo peridot

as the dosing goes up to walk into the

parkinsonian range with parkinsonism

elevated prolactin emia Galacta RIA

amenorrhea and of course long-term

tardive dyskinesia olanzapine is

effective at 10 20 milligrams per

patient per day it can produce

parkinsonism above 20 or 30 milligrams

there is a risk of tardive dyskinesia

which has been reported and there is

weight gain