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Query: CAS:129-03-3 (Cyproheptadine)
 258 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyproheptadine (1, 10 and 100 muM) significantly reduced insulin release from isolated mouse islets in response to glucose. In contrast, 1 mM cyproheptadine induced a large release of insulin into the incubation medium probably due to islet cell damage, since the islets had lost a considerable amount of their protein content. 3',5'-cyclic-AMP-levels of the islets were not significantly affected by 10 muM cyproheptadine in the presence as well as in the absence of theophylline (10 mM). As the inhibitory effect of cyproheptadine on insulin release was correlated with reduced accumulation of calcium-45, the agent may inhibit insulin release by interfering with the calcium handling of the beta-cell.
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PMID:Inhibition o'f insulin release by cyproheptadine: effects on 3',5'-cyclic-AMP-content and 45Ca-accumulation of incubated mouse islets. 17 33

The administration of cyproheptadine (25 mg/kg; i.p.) resulted in an increase of plasma insulin and glucagon (measured using 30 K antibody) 30, 60 and 120 min after injection to fasted rats. This dose of cyproheptadine also induced a hyperglycemia whereas a lower dose (5 mg/kg; i.p.), which did not alter plasma hormone levels, was associated with a hypoglycemia. Fed rats showed a reduction of plasma insulin with a similar elevation of blood glucose after cyproheptadine. Administration of an exogenous load of arginine resulted in increases of plasma insulin and glucagon of a greater magnitude than induced by cyproheptadine, however, cyproheptadine pretreatment (25 mg/kg) completely suppressed the pancreatic response to the amino acid, resulting in blood hormone levels similar to values seen after cyproheptadine administered alone. Cyproheptadine pretreatment also prevented the hyperinsulinemia and hypoglucagonemia resulting from glucose loading. alpha-Adrenergic receptor blockade (with phentolamine), beta adrenergic receptor blockade (with propranolol) and adrenodemedullation did not alter pancreatic responsiveness to the drug.
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PMID:Paradoxical short-term effects of cyproheptadine on insulin and glucagon release in the rat. 43 34

The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.
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PMID:Improved oral glucose tolerance following antiserotonin treatment in patients with chemical diabetes. 49 87

113 cases of accidental ingestion of cyproheptadine (Nuran) by children have been evaluated. Life threatening alterations have not been observed after doses ranging from 0.3-6.15 (x:1.89) mg per kg of body weight. Somnolence, excitation, hallucinations, ataxia, tachycardia, and muscle twitchings were observed frequently, and occasionally gastric pain, dry mucuous surfaces, mydriasis, and rubeosis of the face were present. Symptoms appeared rapidly after ingestion and generally did not last longer than 6-12 h. When given in therapeutic doses, cyproheptadine reduces the secretion of ACTH, cortisol, prolactin, and growth hormone, lowers blood glucose concentrations, and raises the levels of unesterified free fatty acids. Parents frequently complain about unsatisfactory eating habits of their children, but chronic lack of appetite needing therapeutical attention, in healthy children, is the rare exception. Cyproheptadine is an agent with considerable side effects, and it should be prescribed to children only after very careful deliberation.
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PMID:[Toxicity of cyproheptadine. Side effects and accidental overdosage (author's transl)]. 64 45

Treatment for hyperinsulinism in infants and children can be difficult and has included numerous treatment modalities. This paper reports 16 months of palliative treatment with cyproheptadine and diazoxide in a child with hyperinsulinism initially diagnosed at 6 months of age (her insulin level was 80 microU/mL while her glucose level was 38 mg/dL). She continued to have episodes of staring and alteration in level of consciousness while receiving her usual doses of diazoxide (12 mg/kg) alone. Mean nocturnal glucose values, which were quite low during treatment with diazoxide alone, improved significantly with the addition of cyproheptadine to her therapeutic regimen. Fasted C-peptide values, elevated during diazoxide alone, returned to the normal range with combination treatment for 16 months. Cyproheptadine and diazoxide in combination may be useful for treatment of hyperinsulinism that presents after the neonatal period.
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PMID:Palliative treatment of hyperinsulinism with cyproheptadine and diazoxide. 137 58

Cyproheptadine (CPH) inhibits glucose-stimulated insulin synthesis and secretion, and reversibly depletes pancreatic insulin content in the rat. To examine whether the inhibitory actions of CPH on insulin cell function are linked to the ability of glucose to stimulate insulin synthesis and secretion, studies were performed in two different insulin-producing cell lines. CPH effects were compared in HIT-T15 cells, which respond to glucose with increased insulin synthesis and secretion, and in glucose-unresponsive RINm5F cells. CPH produced similar alterations in both cells lines. After a 48-hr culture period in the presence of 0, 0.1, 1.0 or 10.0 microM CPH, cellular insulin stores and media insulin levels were decreased in a concentration-dependent manner. At 10.0 microM CPH, RIN and HIT cell insulin content declined to 34 and 33% of controls respectively. Cellular insulin returned to control levels 48 hr after removal of CPH. In experiments designed to test a direct inhibitory effect on stimulated insulin secretion, 1 and 10.0 microM concentrations of CPH were found to inhibit glucose-stimulated insulin release from HIT cells, and K+, alanine and glyceraldehyde-stimulated release from RIN cells. CPH was also shown to inhibit insulin biosynthesis in both cell lines at concentrations that did not alter the synthesis of total cellular proteins. All of these alterations in cellular function were shown to occur at CPH concentrations that did not affect cell growth or viability. The results show that the actions of CPH do not appear to be dependent upon the existence of operational glucose signalling mechanisms for insulin synthesis and secretion.
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PMID:Cyproheptadine-induced alterations in clonal insulin-producing cell lines. 219 52

Cyproheptadine (CH) is a serotonin antagonist that increases food intake and body weight. In order to elucidate its mechanism of action on the control of food intake, hunger ratings, pleasure-displeasure to sweet gustatory stimuli and negative alliesthesia induced by a 50 g glucose load were compared in 14 healthy subjects after they had received a placebo or 16 mg of CH. Cyproheptadine did not affect the hunger rating, nor the affective rating in fasted subjects, but it reduced significantly the negative alimentary alliesthesia induced by the glucose load. It was concluded that CH increases food intake more by reducing satiation than by increasing hunger. This is in line with the anti-serotoninergic properties of CH, and the action of serotonin on the control of food intake.
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PMID:Reduction of negative alliesthesia for sweet gustatory stimuli by cyproheptadine, a serotonin antagonist. 234 85

The susceptibility of fetal endocrine pancreas to the diabetogenic action of cyproheptadine was investigated. Cyproheptadine (5 or 11 mg/kg) or water (control) was given orally once daily to pregnant rats on Days 13.5-20.5 or on Days 19.5-20.5 of gestation. Fetuses were obtained by cesarean section 24 hr after the last dose. Serum and pancreatic immunoreactive insulin and serum glucose from maternal and fetal animals were measured. Differences in maternal pancreatic insulin, serum insulin, and glucose between control and treated groups were not detected. In contrast, fetal pancreatic and serum insulin concentrations in animals exposed to 2 or 8 doses of cyproheptadine were less than 50% those of control. Drug treatment did not alter fetal pancreatic glucagon, pancreatic somatostatin, serum glucose, pancreas weight, or body weight. The drug-related depletion of fetal pancreatic insulin was reversible; the level returned to normal 3 days after cessation of the drug treatment. A similar depletion of fetal insulin was observed after 8 oral doses (11 mg/kg) of desmethylcyproheptadine, a metabolite which lacks the antiserotonin-antihistaminic properties of the parent compound. In vitro experiments showed that cyproheptadine inhibited the biosynthesis and release of insulin in fetal rat pancreas. These results indicate that cyproheptadine, when given to pregnant rats using a dose which produces no apparent effects in the maternal endocrine pancreas, causes abnormalities in the function of the insulin-secreting B cells in the fetal endocrine pancreas.
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PMID:Susceptibility of fetal rat endocrine pancreas to the diabetogenic action of cyproheptadine. 352 Sep 54

Severe hypoglycemia and increased deaths were observed among two strains of endotoxin-poisoned mice within 3 to 6 hr after tryptophan injection. Sensitivity to tryptophan could be demonstrated in Rockland Farms mice by 4 hr after endotoxin and in Carworth Farms (CF-1) mice by 10 hr after endotoxin. If allopurinol was given to CF-1 mice concurrently with endotoxin, severe hypoglycemia and increased deaths were observed when tryptophan was given only 4 hr after the bacterial poison. Cyproheptadine, an antiserotonin drug, decreased the number of deaths as well as the depletion of blood glucose in both strains of endotoxin-poisoned mice given a delayed injection of tryptophan. In most instances, liver glycogen was depleted by 8 to 10 hr after endotoxin. Correlation of liver glycogen levels with sensitivity to tryptophan was not as consistent as the correlation between blood glucose levels and hyperreactivity to the amino acid. The data show that severe hypoglycemia is a significant factor which must be considered in resolving the basis for increased deaths among endotoxin-poisoned mice given tryptophan.
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PMID:Carbohydrate metabolism and survival of endotoxin-poisoned mice given tryptophan. 456 58

1 Isolated islets of Langerhans from the rat have been used in studies designed to elucidate the mechanism by which cyproheptadine inhibits insulin secretion. 2 D-Glucose and tolbutamide, both of which require extracellular Ca2+ to produce insulin release, failed to evoke a secretory response from islets pretreated with cyproheptadine. Conversely veratridine, the calcium ionophore A23187 and theophylline, all of which are capable of mobilizing sufficient intracellular Ca2+ to evoke insulin secretion in the absence of extracellular Ca2+, produced similar responses from cyproheptadine pretreated and control islets. 3 Cyproheptadine completely inhibited Ca2+ uptake induced by D-glucose and high Ko+, two agents which depolarize the islet beta-cell membrane, whilst Ca2+ uptake elicited by removal of extracellular Na+ (i.e. Na+-Ca2+ counter transport) was only slightly reduced. 4 A significant increase in Na+ uptake produced by veratridine was sensitive to tetrodoxin but only partially reduced by cyproheptadine. 5 These results suggest that cyproheptadine inhibits depolarization-dependent calcium entry into pancreatic beta-cells.
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PMID:Mechanism by which cyproheptadine inhibits insulin secretion. 700 45


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