Disease relevance of (3-carboxy-2-propionyloxy-propyl)-trimethyl-ammonium

• OBJECTIVES: The aim of this double-blind, placebo-controlled, dose titration, multicenter trial was to assess the efficacy and safety of propionyl-carnitine in intermittent claudication [1].
• In conclusion, L-propionylcarnitine improves walking capacity in patients with peripheral vascular disease, probably acting through a metabolic mechanism [2].
• The effect of L-propionylcarnitine on patients with left ventricular dysfunction (EF < 45%) NYHA class II, symptomatic despite therapy with digitalis and diuretics was evaluated in a phase II parallel, double-blind, randomized, placebo-controlled study [3].
• However, in the adult rat hearts, L-propionylcarnitine given before ischemia and throughout reperfusion was protective by reducing creatine kinase leakage [4].
• 1. The antiarrhythmic effect of L-propionylcarnitine (L-PC) was evaluated in the guinea-pig isolated heart; arrhythmias were induced with hypoxia followed by reoxygenation and by digitalis intoxication [5].

Psychiatry related information on (3-carboxy-2-propionyloxy-propyl)-trimethyl-ammonium

• Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004) [6].

High impact information on (3-carboxy-2-propionyloxy-propyl)-trimethyl-ammonium

• The use of fast atom bombardment mass spectrometry and linked scanning at constant magnetic (B) to electric (E) field ratio identified the acylcarnitine as propionylcarnitine in patients with propionic acidemia [7].
• The results failed to demonstrate that propionylcarnitine had any beneficial effect on the ischaemic myocardium [8].
• Left ventricular shortening fraction and left ventricular ejection fraction showed a significant increase in the L-propionylcarnitine group (respectively P < 0.01 and P < 0.0001) whereas no difference was apparent in the placebo group [3].
• The addition of 1 mM propionylcarnitine failed to cause an anaplerotic effect, but did bring about an oxidation of flavins, probably due to citrate synthase inhibition [8].
• Metabolic effects of propionate, hexanoate and propionylcarnitine in normoxia, ischaemia and reperfusion. Does an anaplerotic substrate protect the ischaemic myocardium [8]?

Chemical compound and disease context of (3-carboxy-2-propionyloxy-propyl)-trimethyl-ammonium

• Superiority of L-propionylcarnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease: an acute, intravenous, double-blind, cross-over study [2].
• We assessed the protective effects of L-propionylcarnitine, a liposoluble analogue of carnitine, in the isolated heart from rats of different ages subjected to global ischemia and reperfusion [4].
• Thus, levo and propionyl carnitine even more appear to be promising agents in the prevention of doxorubicin-related cardiac toxicity [9].
• Indomethacin, a well known prostanoid synthesis blocker, is unable to inhibit the protective activity of propionyl carnitine on endothelin-induced thrombosis after prolonged propionyl carnitine administration, but only a part of this protective activity after propionyl carnitine acute administration [10].
• Moreover, the adenosine increase which follows the administration of some drugs, such as buflomedil and propionylcarnitine, opens new perspectives in the management of leg ischemia [11].

Biological context of (3-carboxy-2-propionyloxy-propyl)-trimethyl-ammonium

• The addition of either 5.5 or 11 mmol X litre-1 L-propionylcarnitine significantly improved the recovery of cardiac output, left ventricular pressure, and dP/dt after 90 min of ischaemia and 15 min of reperfusion [12].
• Postischemic recovery of coronary flow and left ventricular developed pressure were age dependent and were not affected by L-propionylcarnitine, but recovery of heart rate was decreased in neonatal and immature hearts by 10(-4) M and 10(-5) M (p < 0.05), compared with controls (protocol 2) [4].
• The presence of millimolar concentrations of propionyl carnitine decreases purine release and improves cardiac performance as measured by cardiac output and double product (product of heart rate and aortic systolic pressure) [13].
• The effects of L-propionylcarnitine (PC), a derivative of L-carnitine, on action potentials of canine Purkinje fibers in vitro, were studied under acidic conditions (pH 6.9), using conventional microelectrode techniques [14].
• In the control animals, at the end of the second reperfusion period, systemic vascular resistance had increased by 18%, which, however, was not observed in the L-propionylcarnitine-treated pigs [15].

Anatomical context of (3-carboxy-2-propionyloxy-propyl)-trimethyl-ammonium

• In myocytes only L-propionylcarnitine affected palmitate oxidation [12].
• All of these derivatives competitively inhibited L-3H-carnitine transport in isolated cardiac myocytes, but L-propionylcarnitine was the most potent [12].
• When carnitine (10 mM) was added, propionylcarnitine generation represented 65-71% of total propionate utilization in hepatocytes isolated from vitamin B-12--deficient rats [16].
• To identify the effect of L-propionylcarnitine (LPC) on ischemia, 31 fasting, untreated male patients with left coronary artery disease were studied during 2 identical pacing stress tests 45 minutes before (atrial pacing test I [APST I]) and 15 minutes after (APST II) administration of 15 mg/kg of LPC or placebo [17].
• Effect of a single IV administration of l-propionylcarnitine on myocardial microcirculation assessed by coronary flow velocity reserve measurement in patients with systemic sclerosis: A pilot study [18].

Associations of (3-carboxy-2-propionyloxy-propyl)-trimethyl-ammonium with other chemical compounds

• In 14 patients, both treatments improved walking capacity; however, the analysis of variance showed that the increase in maximal walking distance with L-propionylcarnitine was greater than that with L-carnitine (P less than 0.05) [2].
• Under conditions where carnitine partially reversed the inhibitory effect of propionic acid on pyruvate oxidation, formation of propionylcarnitine was documented by using fast-atom-bombardment mass spectroscopy [19].
• Addition of carnitine (10 mM) to hepatocyte incubations increased the rate of propionylcarnitine formation 10- to 20-fold without altering conversion of propionate to CO2 or glucose [16].
• Lactate dehydrogenase leakage was aggravated in the beginning of the reperfusion period by 10 mM L-propionylcarnitine [20].
• The quantitative levels of the various labeled enantiomers of 3-hydroxyisobutyric (3-HIBA), 3-aminoisobutyric (3-AIBA), MMA, and propionylcarnitine were compared following separate intravenous infusions of equimolar doses of [2H8]-valine or [2H4]thymine in this patient and another with methylmalonyl-CoA mutase deficiency [21].

Gene context of (3-carboxy-2-propionyloxy-propyl)-trimethyl-ammonium

• The propionyl carnitine ester also increased the gastric content of reduced glutathione (GSH), besides it increased the enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST) [22].
• For this purpose a mito chondrial lysate was incubated with synthetic 3-oxovalproyl-CoA, carnitine and carnitine acetyltransferase for subsequent monitoring of the formation of propionylcarnitine and pentanoylcarnitine using electrospray ionization tandem MS [23].
• Subsequently, other factors in addition to prostanoids seem to be involved in protective mechanisms of propionyl carnitine on endothelin-induced thrombosis [10].
• It has been reported that L-propionylcarnitine possesses a protective action against heart ischemia-reperfusion injury; however, the antioxidant mechanism is not yet clear [24].
• A double-blind phase II study of propionyl-L-carnitine (CAS 17298-37-2) versus placebo was carried out on a group of 60 patients with mild to moderate (II and III NYHA class) congestive heart failure [25].

Analytical, diagnostic and therapeutic context of (3-carboxy-2-propionyloxy-propyl)-trimethyl-ammonium

• Once the efficacious dose of L-propionylcarnitine was assessed, its effect was compared to that of an equimolar dose of L-carnitine (500 mg i.v.) according to a double-blind, double-dummy, cross-over design [2].
• Enantio- and chemo-selective HPLC separations by chiral-achiral tandem-columns approach: the combination of CHIROBIOTIC TAG and SCX columns for the analysis of propionyl carnitine and related impurities [26].
• High performance liquid chromatography was used to permit specific quantification of propionylcarnitine [27].
• In animal models, administration of the natural derivative, L-propionylcarnitine, may reduce ischemia and improve cardiac function [28].
• The present study investigates whether perfusion with a solution of endothelin-1 in rat isolated kidney can induce the release of histamine, another vasal factor (until now not investigated in relation with endothelin-1) and whether treatment with propionyl carnitine, a compound with vasoprotecting activity, inhibits this release [29].

References