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Heikkila RE, Cohen G. Evaluation of amantadine as a releasing agent or uptake blocker for H3-dopamine in rat brain slices. Eur.  Pharmacol. 20, 156–160 (1972). 27. Baldessarini RJ, Lipinski JF, Chace KV. Effects of amantadine hydrochloride on catecholamine metabolism in the brain of the rat. Biochem. Pharmacol. 21, 77–87 (1972). 28. Gianutsos G, Chute S, Dunn JP. Pharmacological changes in dopaminergic systems induced by longterm administration of amantadine. Eur.  Pharmacol. 110, 357–361 (1985).

While included in the longitudinal treatment early in this diagram, increasing evidence suggests that exercise may potentially slow progression of PD and/or ameliorate symptoms such as gait and balance disturbances through mechanisms distinct and possibly complementary to pharmacological options during all stages of the disease [46–48] . Financial & competing interests disclosure LW Elmer has received honoraria or payments for consulting, advisory services, speaking services or unrestricted educational grants from Lundbeck, Teva Neuroscience and UCB Inc.

Patients using apo­ morphine should be pretreated with 300-mg trimethobenzamide threetimes daily for the first 2 months of use to prevent nausea and vomiting. Another common motor complication in the ‘off-state’ is dystonia, manifested most frequently as flexion of the foot and second through fifth toes with extension of the big toe on the most affected side [12] . In young-onset PD it is commonly seen early in the course of the disease and is thought to be due to abnormal firing of the globus pallidus with underactivity of the D2-mediated striatal output to the globus pallidus externa [4,12,13] .

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