DL-Carnitine ((±)-Carnitin)

Palmitoyl-DL-carnitine has calcium-dependent effects on cultured neurones from rat dorsal root ganglia

1. The effects of palmitoyl-DL-carnitine (0.01 to 1 mM) on whole cell voltage-activated calcium channel currents carried by calcium or barium and Ca(2+)-activated chloride currents were studied in cultured neurones from rat dorsal root ganglia. 2. Palmitoyl-DL-carnitine applied to the extracellular environment or intracellularly via the patch solution reduced Ca2+ currents activated over a wide voltage range from a holding potential of -90 mV. Inhibition of high voltage activated Ca2+ channel currents was dependent on intracellular Ca2+ buffering and was reduced by increasing the EGTA concentration from 2 to 10 mM in the patch solution. Barium currents were significantly less sensitive to palmitoyl-DL-carnitine than Ca2+ currents. 3. The amplitude of Ca(2+)-activated Cl- tail currents was reduced by palmitoyl-DL-carnitine. However, the duration of these Cl- currents was greatly prolonged by palmitoyl-DL-carnitine, suggesting slower removal of free Ca2+ from the cytoplasm following Ca2+ entry through voltage-activated channels. 4. Palmitoyl-DL-carnitine evoked Ca(2+)-dependent inward currents which could be promoted by activation of the residual voltage-activated Ca2+ currents and attenuated by intracellular application of EGTA. 5. We conclude that palmitoyl-DL-carnitine reduced the efficiency of intracellular Ca2+ handling in cultured dorsal root ganglion neurones and resulted in enhancement of Ca(2+)-dependent events including inactivation of voltage-activated Ca2+ currents. The activation of inward currents by palmitolyl-DL-carnitine may involve Ca(2+)-induced Ca2+ release from intracellular stores, or direct interaction of palmitoyl-DL-carnitine with Ca2+ stores.

O-acylation of dl-carnitine chloride

Bioanalysis and enantioseparation of dl-carnitine in human plasma by the derivatization approach

Background: L-carnitine is an over the counter drug, used to treat disorders like cardiomyopathy, skeletal myopathy, hypoglycemia and hyperammonemia. Preparations containing D-carnitine should be avoided by dialysis patients because it has toxic influence on biochemical processes by inhibiting the carnitine acetyltransferase. Therefore, it is of utmost importance to assess and control the content of D-carnitine.
Methods: A HPLC method was developed and validated for determination and enantiomeric resolution of DL-carnitine in human plasma by derivatization approach. (S)-Naproxen-based three derivatizing reagents were synthesized and applied.
Conclusion: The limit of detection values were found to be 1.26 and 1.35 ng ml(-1) for the two isomers. The method is simple, reproducible, and can be used for routine analysis in laboratories for control of enantiomeric purity of carnitine.

Palmitoyl-DL-carnitine is a multitarget inhibitor of Pseudomonas aeruginosa biofilm development

Bacteria growing in biofilms are often in metabolic and physiological states that do not respond well to antibiotics, and thus, are major contributors to chronic diseases. Biofilm inhibitors, therefore, have the potential to be used alone or as adjuvants to conventional antibiotic therapies. Here, we screened a chemically diverse collection of protein kinase inhibitors for molecules that perturb biofilm development. Among the inhibitory molecules identified, palmitoyl-DL-carnitine (pDLC) impaired Pseudomonas aeruginosa and Escherichia coli biofilm formation in a dose-dependent manner. The pDLC affected multiple pathways implicated in P. aeruginosa biofilm development; it stimulated motility, inhibited activity of the Las quorum sensing system, and overrode the biofilm-promoting effects of subminimal inhibitory concentrations of aminoglycosides and high levels of the second messenger, cyclic-di-GMP. Palmitic acid, but not carnitine, inhibited biofilm formation but did not stimulate motility, suggesting that pDLC works through unique mechanisms. The ability to target multiple pathways involved in biofilm formation is desirable in an inhibitor, which makes pDLC an interesting lead for antibiofilm therapies.

Effects of L- and DL-carnitine on patients with impaired exercise tolerance

We designed this study to determine whether orally administered L- and DL-carnitine can improve exercise tolerance in a group of patients with exercise intolerance. Nineteen patients with cardiac disease were randomly divided into 2 groups, an L-carnitine treatment group (n = 9) and a DL-carnitine treatment group (n = 10). Eight additional age-matched patients served as an untreated control group. Subjects in both carnitine treatment groups underwent cardiopulmonary exercise testing on a cycle ergometer in order to determine peak exercise time, peak oxygen uptake (VO2), lactate threshold (LT) and ventilatory threshold (VT) before and after the oral administration of 900 mg/day of L- or DL-carnitine for 2 weeks. Basal values of peak exercise time, peak VO2, LT and VT did not differ significantly among the 3 groups. Peak exercise time and peak VO2 tended to be increased in the L-carnitine treatment group, and tended to be decreased in the DL-carnitine treatment group. Both LT and VT (ml/kg/min) were significantly improved (LT: from 9.7 +/- 0.6 to 10.8 +/- 1.0, p < 0.05; VT: from 9.8 +/- 0.8 to 11.8 +/- 1.9, p < 0.02) by the administration of L-carnitine, while LT was significantly decreased (from 11.0 +/- 2.0 to 9.6 +/- 1.2, p < 0.05) and VT tended to be decreased by the administration of DL-carnitine (from 11.6 +/- 2.0 to 10.8 +/- 2.4). In the untreated control group, no significant changes were observed in the values of exercise tolerance between the 2 series of exercise testings. In neither group did carnitine modify hemodynamic parameters at rest or during exercise. In conclusion, this study demonstrated that L-carnitine increases and DL-carnitine decreases exercise tolerance in patients with impaired exercise tolerance.