Restless legs syndrome (RLS) is defined as the urge to move one's legs, accompanied by unpleasant sensations in one's limbs, and is typically more severe at night. Sleep hygiene measures should be recommended and all causes of secondary RLS such as iron deficiency and medications (antidepressants, antiemetics, antipsychotics, and antihistamines) should be excluded before pharmacological treatment of RLS is initiated. In view of evidence of their efficacy and tolerability, ropinorole, pramipexole, gabapentin, and oral iron should be considered as first-line treatments for RLS. Ropinirole and pramipexole are the only drugs approved for the treatment of RLS in Korea. Ropinirole is metabolized by cytochrome P450 1A2 in the liver. On the other hand, pramipexole is metabolized only to a minor degree, and urinary excretion is the major route of elimination; thus, doses of pramipexole should be reduced in patients with impaired renal functioning. Gabapentin, which is known to be effective for pain and sleep disturbances in patients with RLS, is also secreted unmodified by the kidneys. An oral iron supplement is recommended for patients with low normal serum ferritin levels (< or = 75 ng/mL). Levodopa, pergolide, cabergoline, valproic acid, carbamazepine, and IV iron dextran are classified as second-line treatments. Clonazepam, bupropion, and some opioids can also be used in patients with RLS. In conclusion, pharmacological treatment of RLS should be individualized according to the physical status of patients as well as their RLS symptoms, and augmentation should be carefully monitored when dopaminergic agents are used for long periods.
Amines ; Analgesics, Opioid ; Antiemetics ; Antipsychotic Agents ; Benzothiazoles ; Bupropion ; Carbamazepine ; Clonazepam ; Cyclohexanecarboxylic Acids ; Cytochrome P-450 CYP1A2 ; Dextrans ; Dopamine ; Dopamine Agents ; Ergolines ; Extremities ; Ferritins ; gamma-Aminobutyric Acid ; Hand ; Humans ; Hygiene ; Indoles ; Iron ; Kidney ; Korea ; Leg ; Levodopa ; Liver ; Pergolide ; Restless Legs Syndrome ; Sensation ; Valproic Acid

Gerbil forebrain ischemia/reperfusion(I/R) injury model was used to study the effects of D(1) and D(2) receptor agonists and antagonists on neuronal apoptosis of hippocampal CA1 area. All animals were tested for habituation deficits in an open field test on the 1st, 3rd and 7th days after reperfusion. The animals were then killed, and brains underwent paraffin embedding for hematoxylin-eosin staining, in situ terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) staining and immunohistochemistry (bax, bcl-2). The result of open field test showed that the I/R group was significantly impaired (higher activity scores) when compared with the control group. Pretreatment with pergolide significantly reduced this habituation impairment. Forebrain ischemia for 5 min resulted in extensive CA1 apoptosis on the 3rd and 7th days after I/R injury. About 95% neurons in hippocampal CA1 area entered apoptosis and only 2%-7% pyramidal neurons stayed alive due to an inhibition of bcl-2 expression and an increase in bax expression. Pretreatment of pergolide attenuated neuronal damage caused by transient ischemia. Infusion of pergolide could induce the expression of bcl-2 and reduce the expression of bax. Pretreatment with SKF38393, SCH23390 and spiperone had no effects on these changes in this transient I/R injury model. All these results indicate that pergolide plays an important role in the protection of hippocampal neurons from apotosis through upregulating the expression of bcl-2 protein and reducing the expression of bax protein.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; pharmacology ; Animals ; Apoptosis ; Brain ; physiopathology ; Brain Ischemia ; physiopathology ; Dopamine Agonists ; pharmacology ; Dopamine Antagonists ; pharmacology ; Gerbillinae ; Hippocampus ; physiopathology ; Ischemic Attack, Transient ; physiopathology ; Male ; Neurons ; physiology ; Neuroprotective Agents ; pharmacology ; Pergolide ; pharmacology ; Prosencephalon ; physiopathology ; Proto-Oncogene Proteins ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Reperfusion Injury ; physiopathology ; bcl-2-Associated X Protein