These drugs are defined as indirect acting because they depend on the activity of neurons. Previous animal studies have shown that cocaine occupies or blocks dopamine transporter sites and prevents dopamine from returning, as it normally would, to the brain cells that release it. This allows high concentrations of dopamine to remain available in the brain longer than normal, which is believed to cause the high associated with cocaine use. (Funk & Wagnalls, 1987) Researchers found that high doses of cocaine blocked from 60 to 77 percent of the users' dopamine transporter sites. (Toufexis, 1996) For the user to perceive cocaine's effects, about half of the sites had to be blocked, the study found. (Perkinson, 1994) Metamphetamine, or speed, produces a similar effect, dramatically boosting the supply of dopamine at brain synapses, which results in increased stimulation and feelings of euphoria. New research has also revealed that a chemical in cigarette smoke may keep dopamine in synapses by blocking an enzyme (called monoamine oxidase or MAO) designed to break it down. In contrast, some drugs bypass neurotransmitters altogether and act directly on receptors, and these drugs are called direct acting. Use of these kinds of drugs such as cocaine and amphetamine can lead to very different results in treating the same disease. (Ruden, 1998) As mentioned earlier, people with Parkinson's disease lose neurons that contain dopamine. To compensate for this loss, the body produces more dopamine receptors on other neurons. Indirect agonists are not very effective in treating the disease since they depend on the presence of dopamine neurons. In contrast, direct agonists are more effective because they stimulate dopamine receptors even when dopamine neurons are missing. (Webster, 1994) .
Drugs not only alter the function of dopamine but also the dopamine levels. Some drugs increase dopamine by preventing dopamine reuptake, leaving more dopamine in the synapse.
