From the Guidelines
Restless leg syndrome primarily involves dysfunction in the dopamine system, which is the main neurotransmitter implicated in this condition. The disorder appears to result from impaired dopamine signaling in the brain, particularly in the basal ganglia which controls movement, as evidenced by the American Academy of Sleep Medicine clinical practice guideline 1. Iron deficiency may contribute to this dopamine dysfunction since iron is a cofactor for dopamine production. Other neurotransmitters that may play a role include glutamate and GABA, as their imbalance can affect motor control and sensory processing.
Key points to consider in the pathophysiology of RLS include:
- Dopamine agonists constitute the majority of FDA-approved medications for RLS, but their use can lead to augmentation of symptoms 1
- Iron treatment is an important addition to the management of RLS, particularly in patients with brain iron deficiency 1
- The involvement of other neurotransmitters, such as glutamate and GABA, in the pathophysiology of RLS is less clear, but they may play a role in motor control and sensory processing
Medications that target the dopamine system, such as dopamine agonists, are often effective treatments for RLS, as they work by mimicking dopamine's action in the brain 1. However, the use of these medications must be carefully managed to minimize the risk of augmentation. The use of dopamine agonists, combined with iron supplementation and other treatments, may be an effective approach to managing RLS symptoms, but further research is needed to determine the optimal treatment strategy 1.
From the FDA Drug Label
The precise mechanism of action of ropinirole as a treatment for RLS is unknown, although it is thought to be related to its ability to stimulate dopamine receptors. The mechanism of orthostatic hypotension induced by ropinirole is presumed to be due to a D2-mediated blunting of the noradrenergic response to standing and subsequent decrease in peripheral vascular resistance.
The neurotransmitters involved in Restless Legs Syndrome (RLS) are:
- Dopamine: Ropinirole is thought to stimulate dopamine receptors to treat RLS.
- Norepinephrine: The noradrenergic response is blunted by ropinirole, leading to orthostatic hypotension. 2
From the Research
Neurotransmitters Involved in Restless Legs Syndrome (RLS)
The pathophysiology of RLS is complex and involves multiple neurotransmitter systems. The key neurotransmitters implicated in RLS include:
- Dopamine: Dopaminergic dysfunction is a central feature of RLS, with dopaminergic agents being the primary treatment option 3, 4, 5, 6.
- Iron: Reduced central nervous system iron levels have been linked to RLS, and iron supplementation may improve symptoms and reduce the risk of augmentation 3, 4, 7, 6.
- Other neurotransmitters: Alterations in neurotransmitters such as hypocretins, endorphins, and immune dysfunction and inflammatory mechanisms may also contribute to the development of RLS 7, 6.
Treatment Options for RLS
Treatment for RLS typically involves pharmacological interventions, including:
- Dopamine agonists: Pramipexole, ropinirole, rotigotine transdermal patch, and levodopa are commonly used to treat RLS 3, 4, 5, 6.
- Opioids: Mu-specific opioids, such as codeine, tramadol, and oxycodone, may be used to treat RLS, particularly in severe cases 3, 7, 6.
- Anticonvulsants: Gabapentin, gabapentin enacarbil, and pregabalin may be used as alternative or additional treatments for RLS 3, 7, 6.