Dopamine is a neurotransmitter that is used in all areas of the brain. It is particularly important for regulating the function of the basal ganglia. There are at least five subtypes of dopamine receptors, called D1 through D5; the D1 and D5 subtypes are referred to as "D1-like," while D2, D3, and D4 are referred to as "D2-like." These are grouped in this manner because of the common properties of the receptor effects. In children, dopaminergic medicines are used to treat primary deficiencies of the dopamine system, as in dopa-responsive dystonia or juvenile Parkinson's disease. Certain medications may also be useful for tic disorders or static basal ganglia injury.
L-dopa/carbidopa (Sinemet® and others). If dopamine is taken by mouth, it is rapidly degraded in the intestine and blood and it does not penetrate from the blood into the brain. Therefore, the precursor L-dopa is administered, instead of dopamine. L-dopa is converted to dopamine in blood and in the brain. In order to maximize the effectiveness of L-dopa, it is usually given in combination with a medicine such as carbidopa, which blocks the conversion of L-dopa to dopamine in the blood. Therefore, more L-dopa is transported into the brain, where it is converted to dopamine. The combination of L-dopa and carbidopa is sold in the US under the trade name Sinemet®, among others. L-dopa/carbidopa is the primary treatment for dopa-responsive dystonia (DRD) and juvenile Parkinson's disease. There is also evidence that it may be helpful in some children with cerebral palsy. The side effects of L-dopa include nausea, constipation, and low blood pressure. These side effects can often be controlled by the use of additional carbidopa, domperidone (not available in the US), or other anti-emetic medications. L-dopa is absorbed more rapidly with sugar, and less rapidly with protein. In general, the therapeutic effect and side effects are greatest when it is taken on an empty stomach.
Dopamine Agonists (Parlodel®, Mirapex®, Requip®). Another class of medicines called "dopamine agonists" act similarly to dopamine by directly activating the dopamine receptor. Different agonists have varying activities at the different dopamine receptors; therefore, their effects are subtly different. Dopamine agonists have been very successful in the treatment of adults with Parkinson's disease, but there is less experience with their use in children. Certain rare metabolic diseases may respond to treatment with agonists. In addition, there are a few reports of success with treating tic disorders. Available dopamine agonists include: bromocriptine (Parlodel®); pramipexole (Mirapex®); and ropinirole (Requip®). Side effects are similar to L-dopa, with nausea being the most bothersome. There may also be behavioral changes and occasionally hallucinations.
COMT Inhibitors (Comtan®). A recent class of medications called COMT inhibitors acts by slowing the breakdown of dopamine in the brain. The currently available COMT inhibitor is entacapone (Comtan®). Entacapone prolongs the effectiveness of dopamine and may help to smooth out some of the fluctuations seen as side effects from taking L-dopa and carbidopa. It is used primarily for adult Parkinson's disease. The side effects of this medication have not yet been reported in detail, but concern remains due to the fact that a similar medication (i.e., tolcapone [Tasmar®]) caused severe liver disease in a few adults.
MAO-B inhibitors (selegiline [Eldepryl® and Zelapar®], rasagiline [Azilect®]) slow the breakdown of dopamine in the brain by inhibiting monoamine oxidase type B (MAO-B). MAO-B inhibitors may prolong the action of levodopa or endogenous dopamine. There is very limited experience with these medications in children.
Amantadine is a medicine that was originally intended as an antiviral agent. Subsequently, it was found to have effects similar to dopamine. It probably acts by increasing dopaminergic transmission, as well as blocking glutamate receptors in the caudate and putamen of the globus pallidus. There is very little experience with this medication in children; however, reports suggest benefit for dopa-responsive dystonia (DRD) as well as in some cases of cerebellar disease. Side effects are primarily due to nausea. Behavioral changes have been reported as well as mild anticholinergic effects (similar to trihexyphenidyl).
