How Do Antipsychotic Medications Work?

Drugs that relieve symptoms of schizophrenia alter the activity of specific chemicals, called neurotransmitters, in the brain. These chemicals transmit signals from one brain cell to specific receptors on the next brain cell. Neurotransmitters play a crucial role in the processes responsible for communication between different brain cells.

Interactions with Chemical Messengers

We don't know exactly how it happens, but we do know that mental functions can be altered and adjusted through the use of drugs that affect brain cell function, either by exciting or by inhibiting them, by speeding up or slowing down some of their activity. All psychoactive substances, from socially acceptable drugs such as caffeine to antipsychotic drugs such as clozapine, affect the activity of neurons, although each has its own potency, target in the brain, and psychoactive effect.

Side Effects and Medication Targets

Antipsychotic drugs in general interfere in the functioning of several neurotransmitters and receptors, notably dopamine. Many of the older antipsychotic drugs show strong correlations between their ability to block dopamine receptors in the brain — particularly receptor subtype D-2 — and their ability to relieve psychotic symptoms.

Clozapine targets serotonin receptors more than it does dopamine receptors. Dopamine receptors, like serotonin and other neurotransmitter receptors, are found in different parts of the brain and body. These receptors have different subtypes that are given numbers, such as D-1, D-2, D-3, D-4, and so on. Each of the subtypes has a different function. Dopamine D-2 receptors control body movements; if they are blocked, the tremors associated with Parkinson's disease can result. Since clozapine has less of an effect on the D-2 receptors, it does not cause symptoms like Parkinson's disease, but it does have very strong antipsychotic actions. It also interacts with other receptors, not only those specific to dopamine and serotonin. These interactions seem to account for some of the side effects that may occur with clozapine, including drowsiness, constipation, difficulty urinating, and possible weight gain.

As in other medical specialties, we still do not fully understand how these medications work. Some research, however, suggests they block dopamine receptors in one area of the brain that causes psychotic symptoms without blocking them in other areas. This may explain why some newer antipsychotic medications do not cause some of the undesirable side effects that older medications do.

Ziprasidone is an example of a second generation or atypical antipsychotic that blocks serotonin receptors as well as dopamine receptors. This compound has other interesting pharmacological properties that give it additional therapeutic value: it is fairly good at preventing norepinephrine and serotonin, two neurotransmitters linked to depression, from being taken up into neurons after they have been released.

Ziprasidone thus prolongs the action of these two neurotransmitters by extending their stay in the gap between neurons, where they continue to stimulate their respective receptors. Consequently, some newer medications like Ziprasidone are useful for patients who have symptoms of depression in addition to their symptoms of schizophrenia.

This is only a small example of the many chemical activities these drugs have, and it is an oversimplification of the chemical imbalance that appears to be present in schizophrenia. Nevertheless, it is a basis for beginning to understand the actions of antipsychotic medications.

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