Disease relevance of pantethine

• Metabolism of pantethine in cystinosis [1].
• The relationship between hypercholesterolemia and lipid metabolism in the arterial wall and effects of pantethine are discussed on the basis of these results [2].
• An NADH-linked disulfide reductase specific for disulfides containing pantethine 4',4"-diphosphate moieties was purified 23,000-fold to homogeneity from spores of Bacillus megaterium [3].
• Effectiveness of long-term treatment with pantethine in patients with dyslipidemia [4].
• However, the concentration of plasma prolactin fell by 48 and 67%, when pantethine was injected i.p. at 0.5 and 1.0 g/kg body weight, after 4 h [5].

Psychiatry related information on pantethine

• Dose- and time-response effects of pantethine on open-field behavior, and on central neurotransmission in rats [6].
• It might be that the striatal dopaminergic transmission, modified by administration of pantethine, plays some role in the higher locomotor activity induced by the substance [7].

High impact information on pantethine

• Pantethine was rapidly hydrolyzed to pantothenic acid and cysteamine; we could not detect pantethine in plasma after oral administration [1].
• Pantothenate pharmacokinetics after orally administered pantethine followed an open two-compartment model with slow vitamin elimination (t1/2 = 28 h) [1].
• This phenotype was genetically complemented in aaBB siblings of the progeny and chemically complemented by pantethine [8].
• The effects of pantethine on cholesterol and fatty acid metabolism were investigated in isolated rat hepatocytes [9].
• Pantethine, a stable disulfide precursor of pantetheine, has been reported to increase intracellular concentration of cysteamine in cultured fibroblasts of patients with cystinosis [10].

Chemical compound and disease context of pantethine

• We conclude that pantethine is probably less effective than cysteamine in the treatment of nephropathic cystinosis and should only be considered in cases of cysteamine intolerance [1].
• The authors conclude that pantethine (a drug entity related to the natural compound, pantetheine) represents a valid therapeutic support for patients with dyslipidemia not amenable to satisfactory correction of blood lipids by diet alone [4].
• The hypolipidemic effects of pantothenic acid derivatives (phosphopantothenate, panthenol and pantethine) were studied in mice with hypothalamic obesity [11].

Biological context of pantethine

• At least in 3 independent experimental models, the lipomodulating effect of pantethine appears instead to be mediated by the hydrolysis product cysteamine [12].
• To determine whether this effect was caused by drug-altered food intake, we have measured food and water intake in pantethine-injected rats in the fed and fasting state [13].
• Effects of pantethine supplementation to diets with different energy cereals on hepatic lipogenesis of laying hens [14].
• Cysteamine administered in a dose of 1.95 mM/kg subcutaneously (SC) markedly reduced several open-field behaviors (locomotion, rearing, grooming and defecation), while pantethine, administered in an equimolar dose, reduced the locomotion only [15].
• We have treated 22 diabetic patients on dialysis (8 on hemodialysis and 14 on continuous ambulatory peritoneal dialysis) suffering from hyperlipemia with pantethine, a physiological substance and coenzyme A precursor in the Krebs cycle [16].

Anatomical context of pantethine

• Three hours after pantethine treatment, the oxytocin content in the posterior pituitary and the hypothalamus was markedly reduced with all doses of the drug [17].
• Total lipoprotein lipase activity per g of adipose tissue increased in pantethine-treated rats compared with controls [18].
• There were no significant differences in liver weight, rate of egg production, and egg weight among dietary treatments. these results suggest that dietary pantethine is effective in reducing the accumulation of liver and abdominal fat in laying hens fed a CS diet [14].
• Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system [19].
• In three separate experiments, rats allowed free access to food until the morning of study showed significant increased food intake accompanied by an increased stomach content (at 4 hr) of both food and water following the IP injection of pantethine [13].

Associations of pantethine with other chemical compounds

• Both glutathione and pantethine (1 or 2 mM) strongly inhibited the appearance of higher molecular weight peptides [20].
• Effects of pantethine on cholesterol synthesis from mevalonate in isolated rat hepatocytes [21].
• Acetaldehyde (45 microM) added in vitro to whole blood and plasma obtained 1 hr after pantethine administration disappeared as the incubation continued similarly as with blood and plasma obtained prior to pantethine treatment [22].
• The exact mechanism of action of pantethine on oxytocin and vasopressin remains to be elucidated [17].
• It is possible that the peptide did not reach at the receptor sites in a sufficient concentration because of the reduced endogenous somatostatin content, or that the pantethine-induced noradrenaline depletion is connected with the ineffectiveness of somatostatin [15].

Gene context of pantethine

• This study investigated the effect of pantethine on oxytocin and arginine vasopressin content in the posterior pituitary and hypothalamus [17].
• The depletion of plasma prolactin by pantethine in oestrogen-primed hyperprolactinaemic rats [5].
• The pantethine action observed only in nonflushing subjects might be due to an accelerated oxidation of acetaldehyde by the activation of low Km ALDH by pantethine-related metabolites formed in the liver [22].
• Pantethine, a somatostatin depleting agent, increases food intake in rats [13].
• Lowering effect of pantethine on plasma beta-thromboglobulin and lipids in diabetes mellitus [23].

Analytical, diagnostic and therapeutic context of pantethine

• In the lenses of animals protected from protein aggregation and opacification by administration of 1.5 mmol kg-1 pantethine, the pattern of proteins in SDS-PAGE gels resembled the pattern for proteins from transparent lenses of normal untreated animals and loss of cytoskeletal proteins was prevented [24].
• Pantethine improves the lipid abnormalities of chronic hemodialysis patients: results of a multicenter clinical trial [25].
• In several animal models, preliminary studies have indicated that pantethine may inhibit cataract formation [26].
• Application of pantethine 5 X 10(-3) Gm/ml under hypoxic perfusion prolonged action potential duration and effective refractory period significantly [27].
• Following pantethine, the ambulation increased during the later tests (60 min, 240 min, 24 hr) [28].

References