the neuroleptic malignant syndrome. Faecal transplants may have a beneficial impact on symptoms. History The positive albeit modest effects of anticholinergic alkaloids obtained from the plant of the belladonna were described during the 19th century by Charcot, Erb, and others. Modern surgery for tremor, consisting of the lesioning of some of the basal ganglia structures was first tried in 1939, and was improved over the following 20 years. Before this date, surgery consisted in lesioning the corticospinal pathway with paralysis instead of tremor as result. Anticholinergics and surgery were the only treatments until the arrival of levodopa, which reduced their use dramatically. Levodopa was first synthesized in 1911 by Casimir Funk, but it received little attention until the mid-20th century. It entered clinical practice in 1967, and the first large study reporting improvements in people with Parkinson's disease resulting from treatment with levodopa was published in 1968. Levodopa brought about a revolution in the management of PD. By the late 1980s deep brain stimulation emerged as a possible treatment, and it was approved for clinical use by the FDA in 1997. Research directions No new PD treatments are expected in the short term, but several lines of research are active for new treatments. Such research directions include the search of new animal models of the disease, and the potential usefulness of gene therapy, stem cells transplants, and neuroprotective agents. Animal models The tragedy of a group of drug addicts in California in the early 1980s who consumed a contaminated and illicitly produced batch of the synthetic opiate MPPP brought to light MPTP as a cause of parkinsonian symptoms. Other predominant toxin-based models employ the insecticide rotenone, the herbicide paraquat, and the fungicide maneb. Models based on toxins are most commonly used in primates. Transgenic rodent models also exist. Gene therapy Present treatments of Parkinson's disease provide satisfactory disease control for most early-stage patients. However, present gold-standard treatment of PD using levodopa is associated with motor complications, and does not prevent disease progression. More effective and long-term treatment of PD are urgently needed to control its progression. In vivo gene therapy is a new approach for treatment of PD. The use of somatic-cell gene transfer to alter gene expression in brain neurochemical systems is a novel alternative conventional treatment. Gene therapy is currently under investigation. It involves the use of a noninfectious virus to shuttle a gene into a part of