Objective: To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies.Background: While safe intravenous (IV) use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA) has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND) application is required, including a comprehensive review of toxicity data.Methods: Over 200 articles referring to IV levodopa were examined for details of administration, pharmacokinetics, benefit, and side effects.Results: We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959–1960 before the development of peripheral decarboxylase inhibitors. At least 2760 subjects have received IV levodopa, and reported outcomes include parkinsonian signs, sleep variables, hormone levels, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson's disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis.Conclusion: At least 2760 patients have received IV levodopa with a safety profile comparable to that seen with oral administration.

Caldesmon is a heat-stable protein found in both muscle and non-muscle tissue. It binds to a number of contractile and cytoskeletal proteins and may be involved in regulating acto-myosin interaction in smooth muscle cells and/or the assembly of microfilaments in muscle and non-muscle cells. We have shown previously that caldesmon is localized at the Z-lines in adult cardiac myocytes and that both the low-and high-molecular-weight forms ( l -caldesmon and hcaldesmon, respectively) are present in atrial and ventricular myocytes. Here we examined the expression of caldesmon and its localization in freshly isolated cardiac myocytes during postnatal development and when these myocytes were grown in culture. We found that l -caldesmon is expressed in both neonatal and adult rat ventricular myocytes.The expression of h -caldesmon, however, was not detected in myocytes from newborn animals but increased during the first 2 weeks of postnatal development. Caldesmon was generally not co-localized with α -actinin at the Z-lines in neonatal myocytes but became increasingly more so during the first 2 weeks of postnatal development. When myocytes from 5-and 10-day-old rats were grown in primary culture, h -caldesmon expression decreased and caldesmon could not be detected at the Z-lines in the cultured cells. These results indicate that caldesmon plays a role at the Z-lines in adult cardiac myocytes; however, its localization at the Z-lines is not necessary for the prenatal development that occurs at these sites or for the establishment of a contractile phenotype in cultured cardiac myocytes.

Objective: To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies.

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