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In the 1980s, a pilot preclinical study on two rat and monkey PD models 16 and two independent clinical cases 17,18 showed that intracerebroventricular (i.c.v.) administration of dopamine improved motor symptoms, but also resulted in tachyphylaxia, possibly owing to dopamine oxidation despite the use of a preservative solution (sodium metabisulfite), precluding the therapeutic development of this concept