The two work together to increase dopamine levels in the striatum and prefrontal cortex. Methylphenidate mainly inhibits dopamine and noradrenaline reuptake by blocking presynaptic transporters, and levodopa increases the amount of dopamine, generally improving hypokinesic gait. Some patients, however, have adverse reactions of nausea and headache to the treatment and the long-term effects of the drug treatment still need to be assessed. Stem cells
New treatments include increasing the number of dopamine cells by transplanting stem cells into the basal ganglia or stimulating endogenous stem cell production and movement to the basal ganglia. The successful integration of stem cells can relieve hypokinetic symptoms and decrease the necessary dose of dopaminergic drugs. However, a variety of complications, including possible tumor formation, inappropriate cell migration, rejection of cells by the immune system, and cerebral hemorrhage are possible, causing many physicians to believe the risks outweigh the possible benefits. NOP receptor antagonists
Another treatment, still in an experimental stage, is the administration of nociception FQ peptide (NOP) receptor antagonists. This treatment has been shown to reduce hypokinesia in animal studies when increasing nociception FQ in the substantia nigra and subthalamic nucleus. Low doses can be taken with dopaminergic treatment to decrease the amount of L-dopa needed, which can reduce its long-term side effects and improve motor performance. Dance therapy
Dance therapy has also been shown to reduce hypokinesic movements and rigidity, though targeted more at the muscular aspects of the disorder than the neural activity. Associations
Cognitive impairment
Bradykinesia has been shown to precede impairment of executive functions, working memory, and attention.
1978 Genentech produces biosynthetic human insulin in Escherichia coli bacteria using recombinant DNA techniques, licenses to Eli Lilly
1981 Novo Nordisk chemically and enzymatically converts porcine to human insulin
1982 Genentech synthetic human insulin (above) approved
1983 Eli Lilly and Company produces biosynthetic human insulin with recombinant DNA technology, Humulin
1985 Axel Ullrich sequences a human cell membrane insulin receptor. 1988 Novo Nordisk produces recombinant biosynthetic human insulin
1996 Lilly Humalog "lispro" insulin analogue approved. 2000 Sanofi Aventis Lantus insulin "glargine" analogue approved for clinical use in the US and Europe. 2004 Sanofi Aventis Apidra insulin "glulisine" insulin analogue approved for clinical use in the US. 2006 Novo Nordisk Levemir "detemir" insulin analogue approved for clinical use in the US. Medical uses
Insulin is used to treat a number of diseases including diabetes and its acute complications such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. It is also used along with glucose to treat high blood potassium levels. Use during pregnancy is relatively safe for the baby. Insulin was formerly used in a psychiatric treatment called insulin shock therapy. Side effects
Some side effects are hypoglycemia (low blood sugar), hypokalemia (low blood potassium), and allergic reactions. Allergy to insulin affected about 2% of people, of which most reactions are not due to the insulin itself but to preservatives added to insulin such as zinc, protamine, and meta-cresol. Most reactions are Type I hypersensitivity reactions and rarely cause anaphylaxis. A suspected allergy to insulin can be confirmed by skin prick testing, patch testing and occasionally skin biopsy.