Tardive Dyskinesia

Dopamine & Tardive Dyskinesia

Dopamine is commonly known as a chemical produced by the brain that relates to the sensation of pleasure. Dopamine regulates virtually all bodily functions, including eye movement, heartbeat and breathing. Various types of dopamine (there are several) must exist in carefully regulated amounts in order for these functions to be properly controlled.

With too little dopamine movement becomes difficult. Parkinson's disease is one result of low levels of dopamine. Too much dopamine results in hyperactivity and an inability to remain still. The most extreme form of this is tardive dyskinesia.

Biochemistry and Function of Dopamine

Dopamine is defined as a catecholamine. This means that it is a hormone functioning as a neurotransmitter. The body's nervous system is a sophisticated communication network with the brain sending signals to the various systems through electrochemical impulses. These signals travel through the nerves to the terminals, where they interface with receptors on the surface of cells. In order for those signals to pass from the nerve endings, or synapses, to the cell receptors, dopamine — in very specific amounts — must be present. Dopamine also affects emotional state, perceptions, behavior and cognitive thinking.

Dopamine activates pleasure centers in the brain. Under normal circumstances, just enough dopamine is present to give a general sense of health and well-being. In excess amounts, when dopamine receptors are temporarily blocked and this substance builds up in the synapses, it can make a person feel really good... at least temporarily. Stimulants such as caffeine, amphetamines and cocaine slow down the movement of dopamine across receptors, resulting in increased energy and a sense of false euphoria.

Antipsychotics and Dopamine

Certain forms of mental illness, such as schizophrenia and bipolar disorder, have been attributed to excess amounts of dopamine in the system. In the past, doctors in the U.S. and Britain used electroshock and insulin therapy to treat these conditions. In extreme cases, a surgical procedure, known as frontal lobotomy, was used to kill off the part of a patient's brain that controls emotion and higher cognitive skills.

The introduction of Chlorpromazine (first marketed in the U.S. under the brand name Thorazine© by Smith Kline & French — known today as GlaxoSmithKline) in 1954 was hailed by the psychiatric community as a breakthrough. Chlorpromazine (CPZ) was followed by many more medications in subsequent decades.

Little thought or concern was given to the possibility of side effects until the early 1960s, when the number of patients suffering from tardive dyskinesia symptoms began to increase dramatically.

The D3 Receptor Gene

One problem lies in the fact that while the dopamine receptor involved in emotion and behavior is very specific, the drugs used to control them are not always successful in targeting the receptor. Often, the substances in psychoactive drugs affect a range of dopamine receptors — including those for regulating voluntary muscle function.

The dopamine receptor identified as D3 is one associated with the older regions of the brain. This indicates that it plays a significant role in the more intense, "primitive" emotional states such as fear and rage. As such, it is targeted by psychoactive medications.

Unfortunately, these medications wind up affecting other dopamine receptors This can cause the symptoms associated with tardive dyskinesia, and in some cases, suicidal and/or violent behavior. Although some alternatives and dopamine agonists (drugs that help to restore normal levels of dopamine) have been of some use in treating tardive dyskinesia, the best treatment found thus far is prevention.