Pantethine Abstracts

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The following is a collection of pantethine abstracts from published scientific research and papers. Integratedhealth.com has designed Pantethine Plus with this research in mind.

(REFERENCE 1 OF 24)

Prisco D Rogasi PG Matucci M Paniccia R Abbate R Gensini GF Neri Serneri GG

Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia.

In: Angiology (1987 Mar) 38(3):241-7

In a single-blind, crossover, completely randomized study, the effects of oral treatment with pantethine or placebo on fatty acid composition of plasma and platelet phospholipids were investigated in 10 IIa hyperlipoproteinemic patients. A significant decrease of total cholesterol and total phospholipids was observed both in plasma and in platelets after a twenty-eight-day treatment. In plasma, pantethine induced a decrease of the ratio sphingomyelin/phosphatidylcholine. Moreover, a relative increase of n3-polyunsaturated fatty acids both in plasma and in platelet phospholipids and a decrease of arachidonic acid in plasma phospholipids were observed. These results indicate that pantethine can affect plasma and platelet lipid composition with possibly favorable influences on the determinants of cell membrane fluidity.

 

(REFERENCE 2 OF 24)

Reichlin S Bollinger-Gruber JA

Pantethine, a cysteamine precursor, depletes immunoreactive somatostatin and prolactin in the rat.

In: Endocrinology (1985 Aug) 117(2):492-5

Pantethine, a stable disulfide precursor of pantetheine, has been reported to increase intracellular concentration of cysteamine in cultured fibroblasts of patients with cystinosis. In order to determine whether pantethine acts like cysteamine in bringing about depletion of immunoreactive somatostatin (IRS) in rat neural and gastrointestinal tissues and depletion of immunoreactive PRL (IRPRL) in the anterior pituitary, groups of male rats were given pantethine by ip injection at a dose of 0.264 mM or 0.528 mM/100 g body weight or normal saline and killed 4 h later. The interval chosen corresponds to the time of maximum effect after oral cysteamine administration. In cerebral cortex, hypothalamus, duodenal and gastric mucosa, and pancreas, IRS was uniformly depressed by 50% or more as compared with control rats, the most striking changes occurring in the hypothalamus where there was a 64% depletion at the higher dose of drug. Both dosage levels depleted IRPRL in pituitary and serum. At the higher dose, IRPRL was reduced by approximately 85% in the pituitary and 75% in the serum. These findings support the hypothesis that pantethine administration leads to an accumulation of cysteamine within cells throughout the body and that the cysteamine so formed depletes IRS and IRPRL.

 

(REFERENCE 3 OF 24)

Butler JD Zatz M

Pantethine and cystamine deplete cystine from cystinotic fibroblasts via efflux of cysteamine-cysteine mixed disulfide.

In: J Clin Invest (1984 Aug) 74(2):411-6

Children suffering from cystinosis, a genetic disease characterized by high levels of lysosomal cystine, are currently being treated with cysteamine to lower the cystine levels in their cells. In fibroblasts from these patients, cysteamine and its disulfide, cystamine, are equally effective in lowering cystine levels. We recently reported that pantethine, a dietary precursor of coenzyme A, depletes cystine from cultured, cystinotic fibroblasts as effectively as cystamine. To determine the mechanism of action of pantethine, and of cystamine, we have compared the fate of [35S]cystine-derived metabolites in the presence and absence of these agents. The results indicate that the ability of pantethine to deplete cystine resides in its being a metabolic precursor of cysteamine. Furthermore, both pantethine and cystamine act by generating the mixed disulfide of cysteamine and cysteine in the lysosomes, which is then rapidly excreted from the cells. The fall in intracellular [35S]cystine caused by these agents was not accompanied by a comparable increase in any intracellular metabolite; rather, it could be accounted for by the appearance of mixed disulfide in the medium. There was no accumulation of mixed disulfide in the cells. Radioactivity in cytoplasmic glutathione was, however, increased by cystamine or pantethine. Thus, cysteamine (formed intracellularly in these experiments) undergoes thiol-disulfide exchange with cystine in the lysosomes, producing cysteamine-cysteine mixed disulfide and free cysteine, which enter the cytoplasm. The free cysteine is available to several pathways, including oxidation to the disulfide or the mixed disulfide, and synthesis of glutathione. The mixed disulfide is excreted from the cell, which ultimately depletes the cell of its excess cystine.

 

(REFERENCE 4 OF 24)

Wittwer CT Gahl WA Butler JD Zatz M Thoene JG

Metabolism of pantethine in cystinosis.

In: J Clin Invest (1985 Oct) 76(4):1665-72

D-Pantethine is a conjugate of the vitamin pantothenic acid and the low-molecular-weight aminothiol cysteamine. Pantethine is an experimental hypolipemic agent and has been suggested as a source of cysteamine in the treatment of nephropathic cystinosis. We treated four cystinotic children with 70-1,000 mg/kg per d oral D-pantethine and studied its metabolism. Pantethine was rapidly hydrolyzed to pantothenic acid and cysteamine; we could not detect pantethine in plasma after oral administration. The responsible enzyme, “pantetheinase,” was highly active in homogenates of small intestinal mucosa and plasma. The Michaelis constant of the rat intestinal enzyme was 4.6 microM and its pH profile showed a broad plateau between 4 and 9. Pantothenate pharmacokinetics after orally administered pantethine followed an open two-compartment model with slow vitamin elimination (t1/2 = 28 h). Peak plasma pantothenate occurred at 2.5 h and levels over 250 microM were seen at 300 times normal. Apparent total body storage of pantothenate was significant (25 mg/kg), and plasma levels were elevated threefold for months after pantethine therapy. Plasma cysteamine concentrations after pantethine were similar to those reported after equivalent doses of cysteamine. However, at best only 80% white blood cell cystine depletion occurred. 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. Serum cholesterol was decreased an average of 14%, which supports the potential clinical significance of pantethine as a hypolipemic agent. Rapid in vivo hydrolysis of pantethine suggests that pantothenate or cysteamine may be the effectors of its hypolipemic action.

 

(REFERENCE 5 OF 24)

Hayashi H Kobayashi A Terada H Nagao B Nishiyama T Kamikawa T Yamazaki N

Effects of pantethine on action potential of canine papillary muscle during hypoxic perfusion.

In: Jpn Heart J (1985 Mar) 26(2):289-96

Pantethine, which is known to be converted to coenzyme A, has been reported to have antiarrhythmic action on experimental cardiac arrhythmias. Using standard microelectrode techniques, the electrophysiological effects of pantethine under hypoxic (95% N2 + 5% CO2) perfusion were studied. Hypoxia decreased resting membrane potential, action potential amplitude and maximum velocity of phase 0 and shortened action potential duration and effective refractory period. Application of pantethine 5 X 10(-3) Gm/ml under hypoxic perfusion prolonged action potential duration and effective refractory period significantly. Prolongation of action potential duration by pantethine might be caused by an increase in intracellular ATP. The findings in this study could be an explanation of the possible antiarrhythmic effects of pantethine.

 

(REFERENCE 6 OF 24)

Yoon SB Kajiyama K Ogura R

[EFFECT OF PANTETHINE ON ADRIAMYCIN-INDUCED CARDIOTOXICITY]

In: Kurume Igakkai Zasshi (1982) 45(8):598-606 (Published in Japanese)

Adriamycin (ADM) is one of the most widely used agents for the treatment of solid tumors. Unfortunately, its clinical use has been compromised by potentially lethal cardiotoxicity. Administration of ADM to rats (4 mg/kg ip for one wk) resulted in the functional and morphological disorders of cardiac mitochondria. The use of pantethine (40 mg/kg) in combination with ADM improved the respiratory responses, ATP synthesis, surface potential of inner membrane and the electron spin resonance intensity of cardiac mitochondria, in parallel with decrease of enhanced lipid peroxidation. Thus, the combination therapy of pantethine with ADM is expected to prevent the ADM-induced cardiotoxicity during cancer chemotherapy. (Author abstract)

 

(REFERENCE 7 OF 24)

Binaghi P Cellina G Lo Cicero G Bruschi F Porcaro E Penotti M

[Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age]

In: Minerva Med (1990 Jun) 81(6):475-9 (Published in Italian)

Cardiovascular diseases are the main cause of death also in women. Their incidence, rapidly growing in the peri-menopausal period, is related to serum levels of total cholesterol and its LDL fraction. It was also shown that the peroxidation of LDL is an additional factor in the genesis of atherosclerotic vascular disease. As long-term treatments with synthetic lipid-lowering drugs may cause undesirable side effects, while pantethine is known to be well tolerated, we treated 24 hypercholesterolemic women (total serum cholesterol greater than or equal to 240 mg/dl), in perimenopausal age (range: 45-55 years, mean +/- SD = 51.6 +/- 2.4) with 900 mg/day of pantethine. This is a precursor of coenzyme A, with an antiperoxidation effect in vivo, and our aim was to confirm its lipid lowering activity in this particular type of patients. After 16 weeks of treatment, significant reductions of total cholesterol, LDL-cholesterol and LDL-C/HDL-C ratio could be observed. No remarkable changes of the main laboratory parameters (fasting blood sugar, B.U.N., creatinine, uric acid) were seen. Efficacy percentages of the treatment were about 80%. None of the patients complained of adverse reactions due to the treatment with pantethine. In conclusion, we suggest that pantethine should be considered in the long-term treatment of lipid derangements occurring in the perimenopausal age.

 

(REFERENCE 8 OF 24)

Arsenio L Bodria P Bossi S Lateana M Strata A

[Clinical use of pantethine by parenteral route in the treatment of hyperlipidemia]

In: Acta Biomed Ateneo Parmense (1987) 58(5-6):143-52 (Published in Italian)

Recent investigations have confirmed the effectiveness and the excellent tolerability of pantethine, a derivative of pantetheine, an essential part of the acetylation coenzyme CoA, administered P.O., in normalizing the blood lipid concentrations of patients with hyperlipidemias. A group of 18 patients with hyperlipidemias (9 M, 9 F), with an average age of 52.6 years, was submitted to pantethine parenteral treatment. After a 20 days wash-out, pantethine (400 mg/day; BID) was administered intramuscularly, for 20 days. Total cholesterol, triglycerides, HDL-cholesterol, apo A-1 and B lipoprotein, uric acid in serum, glycemia, CBC, B.U.N., creatininemia, E.S.R., SGOT, SGPT, bilirubinemia, cardiac frequency, blood pressure and body weight were controlled before and after treatment. The drug showed to have a therapeutic effectiveness by a rapid and significant improvement in the blood lipid pattern with reduction of total cholesterol, triglycerides and apo-B lipoprotein and increase of HDL-cholesterol and apo A-1 lipoprotein. The tolerability of pantethine at the stated dosage and mode of administration was invariably excellent, with non complaints or visible side effects imputable to the test drug. BUN, creatininemia, glycemia, SGOT, SGPT, bilirubinemia, E.S.R., CBC, cardiac frequency and blood pressure readings showed no noteworthy changes throughout the study.

 

(REFERENCE 9 OF 24)

Watanabe A Hobara N Kobayashi M Nakatsukasa H Nagashima H

Lowering of blood acetaldehyde but not ethanol concentrations by pantethine following alcohol ingestion: different effects in flushing and nonflushing subjects.

In: Alcohol Clin Exp Res (1985 May-Jun) 9(3):272-6

A rise in blood acetaldehyde concentrations following alcohol ingestion was significantly inhibited when healthy nonflushing subjects were administered a clinical dose of pantethine orally. However, similar findings were not observed in flushing (alcohol-sensitive) subjects lacking hepatic low Km aldehyde dehydrogenase (ALDH). The blood ethanol concentrations were not altered by this treatment in either flushing or nonflushing subjects. 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. Pantethine-related metabolites, such as taurine, pantetheine, coenzyme A, and pantothenate, activated ALDH in vitro. Hepatic acetaldehyde levels following ethanol loading of rats treated with pantethine were much lower than in untreated rats. 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.

 

(REFERENCE 10 OF 24)

Watanabe A Hobara N Nagashima H

Activation and inhibition of yeast aldehyde dehydrogenase activity by pantethine and its metabolites.

In: Ann Nutr Metab (1986) 30(1):54-7

D-Pantethine-related metabolites, such as taurine, D-pantetheine, coenzyme A and D-pantothenate, activated yeast aldehyde dehydrogenase in vitro. D-Pantethine and cysteamine hydrochloride, however, strongly inhibited the activity of this enzyme.

 

(REFERENCE 11 OF 24)

Vecsei L Widerlov E Alling C

Effects of pantethine, cysteamine and pantothenic acid on open-field behavior and brain catecholamines in rats.

In: Arch Int Pharmacodyn Ther (1989 Jul-Aug) 300:14-21

Cysteamine (1.95 mM/kg) markedly decreased the locomotor, rearing and grooming activities, as well as the number of defecation boluses in an open-field test. An equimolar dose of pantethine reduced the locomotor activity to a lesser extent, but has the same potency in decreasing the number of defecation boluses, whereas pantothenic acid did not affect the behavior of the rats. Cysteamine, and to a lesser extent pantethine, reduced the noradrenaline and increased the dopamine and DOPAC concentrations in the hypothalamus. Pantothenic acid itself did not influence the hypothalamic catecholamine concentrations. These results suggest that the lower efficacy of pantethine compared to cysteamine on both behavioral and neurochemical parameters is probably due to a rate-limiting activity of the enzyme pantetheinase in the conversion of pantetheine to cysteamine.

 

(REFERENCE 12 OF 24)

Vecsei L Widerlov E Ekman R Alling C

Cysteamine and pantethine effects on passive avoidance behavior, shuttle box learning, open-field activity, striatal catecholamines and somatostatin.

In: Arch Int Pharmacodyn Ther (1989 May-Jun) 299:14-27

The effects of cysteamine and pantethine were compared on different behavioral tests and neurochemical parameters in rats. Cysteamine, administered in high dose (3.90 mM/kg s.c.), decreased the locomotor and rearing activities of rats, while it slightly but not significantly increased the avoidance latency in a passive avoidance test. Pantethine, 24 hr after its administration, significantly increased the dihydroxyphenyl acetic acid (DOPAC) levels in the striatum. Cysteamine slightly reduced the DOPAC level without influencing the catecholamine levels in this brain area. The striatal somatostatin concentration was reduced 24 hr after the administration of cysteamine, while pantethine did not influence it. After repeated daily injections of pantethine, the drug facilitated the shuttle box learning process and increased the intertrial and open-field activities of the animals. Cysteamine only slightly increased the locomotion and rearing and did not influence the shuttle box learning. Both pantethine and cysteamine slowed the rate of the “body weight increase” of the animals when compared to a saline-treated group. These findings suggest that the locomotor activation induced by pantethine 24 hr after its administration plays an important role in its behavioral effects. 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.

 

(REFERENCE 13 OF 24)

Cighetti G Del Puppo M Paroni R Galli G Kienle MG

Effects of pantethine on cholesterol synthesis from mevalonate in isolated rat hepatocytes.

In: Atherosclerosis (1986 Apr) 60(1):67-77

Results presented here show that when isolated rat hepatocytes are incubated with increasing concentrations of [2-14C]mevalonolactone, incorporation of the substrate into cholesterol is progressively reduced. Correspondingly, an increase of the incorporation of the substrate into precursors of cholesterol (methyl sterols and squalene) occurs. These effects and the observed inhibition of HMGCoA reductase at high mevalonolactone concentration (0.5 mM) are in agreement with those shown by others in cultured hepatocytes. Since pantethine was reported to affect cholesterol biosynthesis from mevalonate in cultured fibroblasts, effects of its addition to hepatocyte incubations at low and high mevalonolactone concentration were studied. Neither the amount of radioactivity incorporated into cholesterol and in its sterol precursors nor sterol levels were modified by pantethine when a mevalonolactone concentration (0.01 mM) that did not alter the levels of intermediates of cholesterol synthesis was used. Pantethine was shown instead to potentiate the decrease of mevalonate incorporation into cholesterol induced by high concentrations of mevalonolactone (0.5 mM). Decrease of 3-hydroxy-3-methylglutaryl CoA reductase activity induced by 1 mM pantethine was twice that caused by mevalonolactone alone. These results may explain the fact that both in laboratory animals and in humans pantethine administration is effective in reducing cholesterol plasma levels in hyperlipidemic conditions.

 

(REFERENCE 14 OF 24)

Cighetti G Del Puppo M Paroni R Galli Kienle M

Modulation of HMG-CoA reductase activity by pantetheine/pantethine.

In: Biochim Biophys Acta (1988 Nov 25) 963(2):389-93

The ability of pantetheine/pantethine to modulate the activity of HMG-CoA reductase was determined in vitro with rat liver microsomes. The decay of the activity was obtained with pantethine in the 10(-5)-10(-4) M range, whereas stimulation by pantetheine occurred at 10(-3)-10(-2) M, as previously reported for GSSG and GSH, respectively. Inhibition of HMG-CoA by pantethine in isolated liver cells was also investigated by measuring the enzyme activity in microsomes isolated from hepatocytes incubated without or with 1 mM pantethine under conditions previously shown by us to induce inhibition of cholesterol synthesis from acetate. The enzyme amount was not modified by pantethine, but in cells treated with the disulphide, the relative amounts of the thiolic active forms of the enzyme, phosphorylated and dephosphorylated, were decreased to about 1/2 compared to controls.

 

(REFERENCE 15 OF 24)

Donati C Bertieri RS Barbi G

[Pantethine, diabetes mellitus and atherosclerosis. Clinical study of 1045 patients]

In: Clin Ter (1989 Mar 31) 128(6):411-22 (Published in Italian)

After a review of the clinical studies on the treatment of diabetic patients with pantethine, the authors discuss the results obtained in a postmarketing surveillance (PMS) study on 1045 hyperlipidemic patients receiving pantethine (900 mg/day on average). Of these patients, 57 were insulin-dependent (Type I) and 241 were non insulin-dependent (Type II) diabetics. Beyond the epidemiological considerations made possible by a PMS study, the authors show that pantethine brought about a statistically significant and comparable improvement of lipid metabolism in the three groups of patients, with very good tolerability. Pantethine should therefore be considered for the treatment of lipid abnormalities also in patients at risk such as those with diabetes mellitus.

 

(REFERENCE 16 OF 24)

Arsenio L Bodria P Magnati G Strata A Trovato R

Effectiveness of long-term treatment with pantethine in patients with dyslipidemia.

In: Clin Ther (1986) 8(5):537-45

A one-year clinical trial with pantethine was conducted in 24 patients with established dyslipidemia of Fredrickson’s types II A, II B, and IV, alone or associated with diabetes mellitus. The treatment was well tolerated by all patients with no subjective complaints or detectable side effects. Blood lipid assays repeated after 1, 3, 6, 9, and 12 months of treatment revealed consistent and statistically significant reductions of all atherogenic lipid fractions (total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B) with parallel increases of high-density lipoprotein cholesterol and apolipoprotein A. The results were equally good in patients with uncomplicated dyslipidemia and in those with associated diabetes mellitus. 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.

 

(REFERENCE 17 OF 24)

Gensini GF Prisco D Rogasi PG Matucci M Neri Serneri GG

Changes in fatty acid composition of the single platelet phospholipids induced by pantethine treatment.

In: Int J Clin Pharmacol Res (1985) 5(5):309-18

In a single-blind cross-over study the effect of oral treatment with pantethine on plasma and platelet lipid composition was evaluated in 20 patients with dyslipidaemia (7 IIa, 7 IIb and 6 Iv type). In plasma significant decreases of total cholesterol and triglycerides with increase of high density lipoprotein-cholesterol were observed. In platelets pantethine treatment significantly reduced phospholipid and cholesterol content. In addition gas-chromatographic analysis showed a reduction of saturated and monounsaturated and a relative increase of polyunsaturated fatty acid content of platelet phospholipids. A selective relative increase was observed of some n-3 polyunsaturated fatty acids like eicosapentaenoic and docosahexaenoic acid whereas arachidonic acid decreased. The present study indicates a favourable influence of pantethine not only on plasma but also on platelet lipids which could be of value in delaying the development of atherosclerosis in delaying the development of atherosclerosis in dyslipidaemic patients

 

(REFERENCE 18 OF 24)

Bertolini S Donati C Elicio N Daga A Cuzzolaro S Marcenaro A Saturnino M Balestreri R

Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children.

In: Int J Clin Pharmacol Ther Toxicol (1986 Nov) 24(11):630-7

Following a brief outline of current knowledge concerning atherosclerosis and its treatment, the authors describe the results obtained by treating with pantethine (900-1200 mg daily for 3 to 6 months) a series of 7 children and 65 adults suffering from hypercholesterolemia alone or associated with hypertriglyceridemia (types IIa and IIb of Fredrickson’s classification). Pantethine treatment produced significant reduction of the better known risk factors (total cholesterol, LDL-cholesterol, triglycerides, and apo-B) and a significant increase of HDL-cholesterol (signally HDL2) and apolipoprotein A-I. The authors conclude with a discussion of these results and of the possible role of pantethine in the treatment of hyperlipoproteinemia, in view of its perfect tolerability and demonstrated therapeutic effectiveness.

 

(REFERENCE 19 OF 24)

Iida J Nishimura K Ukei S Azuma I

Macrophage activation with pantethine and pantetheine-4′-phosphate.

In: Int J Vitam Nutr Res (1985) 55(4):405-11

Adjuvant activities of pantethine (PaSS) and pantetheine-4′-phosphate (PSH-4′-P) were investigated in mice. By the multiple intraperitoneal administration, both PaSS and PSH-4′-P activated the functions of mouse peritoneal adherent cells and splenic natural killer cells. PSH-4′-P was also effective for the activation of natural killer cells by single injection. In in vitro, PaSS induced interleukin-1 (IL-1) secretion at a low concentration but PSH-4′-P did not. Both PaSS and PSH-4′-P could neither induce interleukin-2 (IL-2) secretion, nor could enhance IL-2 secretion by Con A.

 

(REFERENCE 20 OF 24)

Hiramatsu N Kishida T Natake M

Effects of dietary pantethine levels on drug-metabolizing system in the liver of rats orally administered varying amounts of autoxidized linoleate.

In: J Nutr Sci Vitaminol (Tokyo) (1989 Aug) 35(4):303-13

The effects of dietary pantethine levels on the drug-metabolizing system were investigated under administration of varying amounts of autoxidized linoleate (AL) with rat liver microsomes and S-9 fractions. AL having 800 meq/kg of peroxide value and 1,700 meq/kg of carbonyl value was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25 mg% (normal), and 125 mg% pantethine (sufficient). The contents and activities of the enzymes in the drug-metabolizing system in the rat liver of each pantethinelevel group changed essentially in a similar manner, that is, they were induced at an AL daily dose of 0.2 ml/100 g body weight (i.e., small dose) for 5 successive days and lowered at a daily dose of 0.4 ml/100 g body weight (i.e., large dose) by the same administration period, compared with respective non-AL groups in each of the three pantethine levels. In both non-AL and the small-dose AL, enzyme activities of the electron transfer system in rat liver microsomes, aminopyrine-N-demethylase activity, and metabolic activation of 2acetylaminofluorene in S-9 fractions were significantly higher in the pantethine-deficient group than in the pantethine-normal and sufficient groups. In the large-dose AL, the enzyme activities in the drug-metabolizing system decreased significantly in any pantethine levels, though the survival rate of the rats was higher in the pantethine-sufficient group than in the pantethine-normal groups. The results suggest that the pantethine relieves the effect of dosed AL on the drug-metabolizing system in rat liver.

 

(REFERENCE 21 OF 24)

Ong GL Miaskowski C Haldar J

Changes in oxytocin and vasopressin content in posterior pituitary and hypothalamus following pantethine treatment.

In: Life Sci (1990) 47(6):503-6

Pantethine, a cysteamine precursor, depletes somatostatin in the cerebral cortex and hypothalamus and prolactin in the anterior pituitary and hypothalamus. This study investigated the effect of pantethine on oxytocin and arginine vasopressin content in the posterior pituitary and hypothalamus. Male Long-Evans rats were injected intraperitoneally with escalating doses of pantethine (i.e., 146.7 mg, 293.4 mg and 586.6 mg/100 gm body weight). Hormone content was determined by radioimmunoassay. Three hours after pantethine treatment, the oxytocin content in the posterior pituitary and the hypothalamus was markedly reduced with all doses of the drug. Vasopressin content in the posterior pituitary and hypothalamus was decreased but to a lesser extent than oxytocin and only with the highest dose of pantethine. Pantethine may act to reduce oxytocin and vasopressin content through intracellular conversion to cysteamine. The exact mechanism of action of pantethine on oxytocin and vasopressin remains to be elucidated.

 

(REFERENCE 22 OF 24)

Vecsei L Widerlov E Ekman R Alling C

Dose- and time-response effects of pantethine on open-field behavior, and on central neurotransmission in rats.

In: Pharmacol Biochem Behav (1990 Jan) 35(1):165-70

In this study the dose- and time-related effects of pantethine on open-field behavior and central neurotransmissions were investigated in rats. Pantethine administered in low doses (0.48-0.96 mM/kg SC) only marginally influenced the activity of the animals, but induced a significant decrease of hypothalamic noradrenaline level without influencing the concentrations of dopamine and DOPAC. Injected in higher doses (1.95-3.90 mM/kg SC), the compound produced a marked depression of both open-field activity and noradrenaline levels, but increased the concentrations of dopamine and DOPAC in the hypothalamus. Twelve hr after the administration of the substance, its effect was attenuated, and 24 hr after the treatment neither the behavioral nor the monoamine parameters differed significantly from the control values. Concerning the somatostatin, pantethine administered in high doses (1.95-3.90 mM/kg SC) decreased the striatal concentration of somatostatin 4 hr after the injection, and this effect was attenuated 24 hr after the treatment. These data suggest that the pantethine-induced behavioral changes are correlated with its effect on central catecholaminergic and somatostatinergic transmission.

 

(REFERENCE 23 OF 24)

Vecsei L Widerlov E

Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system.

In: Prog Neuropsychopharmacol Biol Psychiatry (1990) 14(6):835-62

Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington’s disease, prolactin-secreting adenomas) indications in clinical practice. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson’s disease, instead of cysteamine) are discussed.

 

(REFERENCE 24 OF 24)

Nagiel-Ostaszewski I Lau-Cam CA

Protection by pantethine, pantothenic acid and cystamine against carbon tetrachloride-induced hepatotoxicity in the rat.

In: Res Commun Chem Pathol Pharmacol (1990 Feb) 67(2):289-92

The daily ip administration of pantethine (500 mg/kg), pantothenic acid (100 mg/kg) or cystamine (50 mg/kg) for 5 days conferred significant protection against the hepatotoxic and peroxidative actions of a 0.5 mL/kg ip dose of CCl4 in rats. All three treatments lessened the increases in serum ALT and liver TBARS values, and the reductions in serum triglyceride levels, and prevented the development of hepatic steatosis caused by the halocarbon. Pantethine was found to offer the greatest protection.