The Potentially Irreversible Effects of Antipsychotics on Brain Receptors (Study Overview)

Introduction

We all know that antipsychotics have been reported to have long term effects? But, do they really?

When truly altruistic psychopharmacologists study these drugs the effects of antipsychotics on brain receptors reveal a harsh truth. Studies show that haloperidol and risperidone don't just change brain function temporarily, they do so permanently. Which in my opinion paints a grim picture of the lasting and potentially harmful impact these medications have on crucial brain receptors. I will be using information from two studies.

Of course this is information from two studies, which is very limiting. But, monetarily driven pharmacologists don’t traditionally report on these negative side effects, so I’m working with what I can.

Lesson in receptors part 1

First, a lesson in receptors. Sigma receptors are a type of protein cell surface found in various tissues, including the brain. They are fairly unique receptors, different from typical receptors like those for neurotransmitters. Sigma receptors are involved in several functions like neuroprotection, neurotransmitter release modulation, memory and learning, and cellular survival.

Study 1: Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells

Study 1 reveals the impact of haloperidol on sigma-1 receptors, crucial for various brain functions. After a single injection, haloperidol caused a marked decrease in these receptors, taking over 30 days to recover. Its metabolite, haloperidol-metabolite II, permanently blocked sigma-1 receptors in guinea pig brains and human cells, hinting at similar impacts in humans. This irreversible inactivation of receptors could lead to prolonged effects even after stopping haloperidol use.

Lesson in receptors part 2

Now, for the next receptor, h5-HT7 a serotonin receptor that has been implicated in regulation of mood, sleep regulation, learning and memory, and control of smooth muscle contraction. But, my past two explanations are both are over generalized and these receptors are extremely complicated.

Study 2: Risperidone Irreversibly Binds to and Inactivates the h5-HT7 Serotonin Receptor

In Study 2, risperidone showed a unique mechanism against h5-HT7 receptors, rendering them completely unresponsive to serotonin for at least 24 hours after removal of the drug. When risperidone interacts with the h5-HT7 receptor, they cause a change in its shape that is not easily reversed. This means that even after the drug is removed from the system, the receptor remains in this altered state for a significant amount of time. This irreversible interaction with the receptor might indicate a broader effect on G-protein-coupled receptors or GPCRs, potentially altering essential brain signaling. It suggests that certain receptors, like the h5-HT7 receptor, might have unique vulnerabilities to specific drugs, leading to long-lasting effects on their function.

“These results indicate that the h5-HT7 receptor may possess unique structural features that allow certain drugs to induce a conformation resulting in an irreversible interaction in the intact membrane environment. This may indicate that the h5-HT7 receptor is part of a subfamily of G-protein-coupled receptors (GPCRs) possessing this property or that many GPCRs have the potential to be irreversibly blocked, but only select drugs can induce this effect.” -Risperidone Irreversibly Binds to and Inactivates the h5-HT7 Serotonin Receptor

Such irreversible deactivation, seen with antipsychotics like haloperidol and risperidone, can disrupt vital brain functions. The long-lasting impact on receptor activity suggests caution, as it could lead to persistent changes in brain chemistry, affecting mood, cognition, and overall mental well-being. These findings emphasize the need for a thoughtful approach to prescribing antipsychotic medications, considering the potential long-term consequences on brain receptors.

I’d also like to mention again these studies are few and far between since it’s not very monetarily relevant for psychopharmacologist to prove their medications cause irreversible receptor effects.