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PubMed1988

Treatment of tardive dyskinesia with ceruletide.

1. Seven patients with TD were treated with a single dose of ceruletide 0.8 microgram/kg i.m. 2. EMG and MV were recorded, and the average power spectrum was computed. 3. Effect of ceruletide on TD within 2 hr after injection was varied (3 cases: inhibitory, 2 cases: facilitatory, 2 cases: no effect). 4. Two patients with severe TD, who showed improvement after a single administration, received repeated administration of ceruletide (0.6 microgram/kg i.m.) and their TD symptoms were recorded on videotape for blind consensus ratings. In both patients ceruletide caused a marked decrease in severity of TD, and the effects lasted for several weeks. 5. The present findings might contribute to further understanding of the role of CCK in the brain and to the treatment of TD.

Adult↗

PubMed1987

Efficacy of ceruletide controlled saline infusion for retained ductal stones after cholecystectomy and exploration of the common bile duct.

The synthetic peptide ceruletide induces maximal relaxation of the sphincter of Oddi. In a preliminary communication, ceruletide controlled saline infusion of the common bile duct (CBD) was found to be effective in promoting the passage of retained ductal calculi after cholecystectomy and exploration of the common bile duct. This paper reports on the further experience with this simple treatment which was administered to 27 patients with retained ductal calculi in 16 different hospitals within the U.K. The success of the procedure was documented by repeat T-tube cholangiography. Passage of stones into the duodenum was documented in 13 patients (48%) with complete clearance in 9 (33%) following one saline infusion/ceruletide treatment. The radiological stone size ranged from 3 to 15 mm. Within this range, there was no correlation between a successful outcome and size of retained stones. The duration of the saline T-tube infusion during ceruletide treatment averaged 54.7/min (SD 14.3). There was no correlation between flow rate of saline through the T-tube and a successful outcome. A significant inverse correlation was observed between the CBD pressure during ceruletide controlled saline T-tube infusion and successful stone passage (chi 2 = 9.9, P less than 0.01). Ampullary impaction by a stone was encountered in one patient. These results are encouraging and indicate that pharmacological dilatation of the sphincter of Oddi together with saline infusion is effective in the management of retained stones after exploration of the common bile duct. This treatment, which does not require any special expertise, should be tried in the first instance before more invasive procedures are used.

Adult↗

PubMed1996

Ceruletide improves event-related potential indicators of cognitive processing in young but not in elderly humans.

The effect of intravenously administered ceruletide, a cholecystokinin (CCK) analogue, on neurophysiologic signs of stimulus processing was tested in 16 young (19-28 years) and 16 aged (70-86 years) healthy subjects. Placebo or 2.5 micrograms ceruletide was infused within 30 minutes according to a double-blind within-subject crossover design. Thereafter, auditory event-related brain potential (AERP) responses to stimuli of an "oddball" task (including the random presentation of frequent standard tones and rare target tones) were recorded. Amplitudes of the P2, P3, and SW components of the AERP were reduced in aged subjects (p < 0.05, p < 0.001, and p < 0.01, respectively), and latencies (from stimulus onset) of the N2 and P3 components were prolonged (p < 0.05 and p < 0.01, respectively). Together, these changes indicate impaired cognitive processing capabilities in aged compared with young subjects. Ceruletide enhanced P3 and also the subsequent slow-wave (SW) component that occurs 500 to 700 ms poststimulus in young subjects (p < 0.05 and p < 0.001, respectively). The peptide did not at all affect AERPs in the elderly subjects. Results demonstrate the capability of ceruletide after systemic administration to enhance central nervous system indicators of cognitive processing such as P3 and SW in young subjects. However, despite the clear effect of the CCK analogue in young subjects, it remained ineffective in the group of aged subjects and, thus, failed to compensate for the decline in AERP signs of working memory functioning in the elderly subjects.

Adult↗

PubMed1993

Influence of potassium concentration in microdialysis perfusate on basal and stimulated striatal dopamine release: effect of ceruletide, a cholecystokinin-related peptide.

The in vivo microdialysis method was used to study the effect of the cholecystokinin-related peptide, ceruletide, on extracellular levels of dopamine (DA) in the striatum following perfusion with various K+ concentrations. Increasing the K+ concentration in the perfusate from 4 to 15 or 17.5 mM did not change basal DA release or release evoked by electrical stimulation of the medial forebrain bundle (MFB). However, when the perfusing solution contained 20 or 30 mM K+, dose-dependent reductions of both basal and MFB-stimulated DA release occurred. Subcutaneous administration of ceruletide at 160 micrograms/kg had no influence on the basal or MFB-stimulated DA release with 4 or 15 mM K+ in the perfusate. However, after perfusion with 17.5 mM K+, ceruletide significantly attenuated the basal and MFB-stimulated DA release. Carbachol (10 microM) locally applied via the dialysis probe also attenuated MFB-stimulated DA release after perfusion with 17.5 mM K+. From these results, we conclude that under appropriate depolarization of striatal DA terminals, ceruletide induces further depolarization and inactivation of nigrostriatal DA terminals. The present data suggest that this effect may be mediated via intrinsic cholinergic neurons in the striatum.

Animals↗

PubMed1990

Influences of the cholecystokinin analog ceruletide on human sleep and evoked potentials.

Two experiments are reported, investigating the effects of the cholecystokinin analog ceruletide on central nervous activation in man. In experiment I, 0.55 micrograms/h ceruletide was infused at a constant rate during the night to study its effects on spontaneous EEG activity during sleep. In experiment II, we examined the effects of a bolus injection of ceruletide (0.5 micrograms) on components of the auditory evoked potential reflecting exogenously provoked central nervous arousal. While ceruletide had no effect on sleep, it attenuated stimulus-induced cortical arousal.

Adult↗

PubMed1983

Protective effects of exogenous secretin on ceruletide-induced acute pancreatitis in the rat.

Unconscious rats given intravenous ceruletide (diethylamine salt of the decapeptide caerulein) in large pharmacologic doses consistently developed moderate acute pancreatitis by 3 h and florid pancreatitis by 6 h. Biochemical serum markers of acute pancreatitis tended to parallel the severity of the pancreatic damage. In 50% of the rats, mesenteric fat necrosis was present, free peritoneal fluid containing massive elevations of trypsinogen and amylase were noted in most animals. Intravenous secretion at a low dose given simultaneously with ceruletide exerted a variable protective effect on the pathological process. A high dose of secretin produced a striking macroscopic, microscopic, and biochemical protective effect on ceruletide-induced pancreatitis. High resolution light microscopy and electron microscopy showed a marked cellular disorganization in the acini of animals treated with ceruletide alone. By contrast, there was a striking apical redirection of zymogen granules in acini of the animals treated with secretin. The results of this study suggest that high dose intravenous secretin may exert a beneficial effect on acute pancreatitis.

Acute Disease↗

PubMed1989

Increased beta-cell secretory responsiveness to ceruletide and TPA in streptozocin-induced mildly diabetic rats.

We examined the effects of various stimuli on immunoreactive insulin (IRI) and glucagon (IRG) release from perfused pancreases isolated from control and streptozocin-induced diabetic (STZ-D) rats. Diabetes was induced by injecting 30 mg/kg STZ into rats fasted for 16-18 h 12-17 days before our experiments. Glucose (11.1 mM) caused a distinct biphasic pattern of IRI release from the control pancreas, whereas the first phase was marginal and the second phase was absent in the diabetic pancreas. Arginine (20 mM)-induced IRI release was similar in both groups, whereas IRG release was greater in the control rats than in the diabetic rats. Thus, this model of STZ-D simulates a certain class of non-insulin-dependent diabetes mellitus (NIDDM). In these diabetic animals, the cholecystokinin (CCK) analogue ceruletide (620 pM) caused a significantly greater increase in IRI release in the presence of 5.6 mM glucose than in the control rats, but ceruletide caused a similar IRG release in both groups. Because CCK and ceruletide stimulate phosphoinositide turnover in pancreatic islets, we examined the effects of carbachol and phorbol ester TPA on IRI release in the presence of 5.6 mM glucose. Carbachol (10 microM), which is thought to generate similar second messengers as ceruletide, induced greater IRI release in diabetic than in control rats. TPA (100 nM) caused a significantly greater increase in IRI release from the diabetic than the control pancreas. Our results demonstrate that the insulin-releasing mechanism involved in protein kinase C activation is enhanced in this model of NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Effects of ceruletide on post-operative intestinal atony: a manometric study.

The effects of ceruletide on jejunal motor activity were studied in seven patients with postoperative intestinal atony. Jejunal pressures were recorded by three perfused catheters with orifices spaced 5 cm apart, the proximal one being positioned 10 cm beyond the ligament of Treitz. Ceruletide (0.05 microgram/Kg i.v.) significantly (p less than 0.0001) increased the number and amplitude of jejunal contractions. The action of ceruletide was most obvious the first 15-minutes after administration, then its effect diminished progressively and ceased after 65-75 minutes. The adverse reactions of ceruletide were minimal and self-limiting.

Adult↗

PubMed1984

[Ceruletide--a sensible adjuvant measure in ERCP?].

The gastro-intestinal hormone Ceruletide is used for diagnostic and therapeutic purposes. Apart from other effects, Ceruletid brings about a relaxation of the Sphincter of Oddi. In the present double-blind study, it was examined on 70 patients whether the effect of this drug can facilitate the cannulation of the Papilla Vateri. Using a dosage of 50 ng/kg body weight Ceruletid in i.m. application the examination time required by the most experienced examiner up to the cannulation of the Papilla Vateri was shortened by half with respect to the collective control group treated with placebo. In the case of less experienced examiners, there was no statistically significant difference in the time of sondage between Ceruletid and the administration of a placebo. Clinical parameters as well as chemical parameters in the laboratory did not reveal any abnormalities. Complications or incompatibilities caused by this drug were not observed.

Adult↗

PubMedDate not supplied

[Cholecystography with ceruletide. Results and evaluation of its routine use].

Cholecystography has been up to day used as unique or first instance examination in patients suspected to have chronic gallbladder diseases. On the other hand, cholecystosonography is proposed with increasing frequence as first examination for simple and rapid detection of cholelithiasis. Results of high standard cholecystography are therefore welcomed in order to assess it present role in respect to diagnostic ultrasounds. On this basis, the authors reports the results of systematic administration of ceruletide in 300 clinically unselected patients with a good opacification at cholecystography. Ceruletide has been demonstrated to be rarely accompanied by a few minor side effects, to have a cholecystokinetic effect more rapid and intense than fatty meal and cholecystokinine and to be followed by frequent diagnostic visualization of cystic duct and choledochus. Small gallbladder stones, diffuse and segmentary cholecystosis and cholecystostasis, with clinical relevance, were easily detected and may be therefore considered as elective indications of ceruletide-assisted-cholecystography. Systemic administration of ceruletide in the course of cholecystography is apt to push its diagnostic possibilities to a maximum extent, allowing appropriate comparison of effectiveness with cholecystosonography in view of their complementary role.

Adolescent↗

PubMed1996

Ultrasonic evaluation of gallbladder emptying with ceruletide.

In order to develop a practical and reproducible method to assess gallbladder function, gallbladder emptying was studied by ultrasound in 27 gallstone patients after i.m. administration of ceruletide (0.3 micrograms/kg), and the procedure was compared to oral cholecystography with fatty meal. Maximal percent gallbladder contraction was reached in all patients 30 min after ceruletide. Maximal percent contractions were 47.5 +/- 27.7 during ultrasound with ceruletide and 33.9 +/- 16.3 during oral cholecystography with fatty meal (p = 0.03). A significant linear relationship was found between the results obtained with the two different procedures (r = 0.57; p = 0.002). Serial ultrasound determinations of gallbladder emptying were performed in 16 patients. Day-to-day variation was below 20% in 11 subjects, and it ranged between 20 and 40% in 5 subjects. Minor side effects were observed in 9 patients. Ultrasound determination of gallbladder emptying after ceruletide appears to be a practical and reliable method to assess gallbladder function.

Adult↗

PubMed1984

Evidence for sphincter dysfunction in patients with gallstone associated pancreatitis: effect of ceruletide in patients undergoing cholecystectomy for gallbladder disease and gallstone associated pancreatitis.

The functional activity of the sphincter of Oddi complex has been examined by ceruletide manometry in patients undergoing cholecystectomy with a normal peroperative cholangiogram. In Group I (n = 14), which included patients with previous acute cholecystitis/biliary colic, the sphincter activity appeared to be normal and responded to intravenous ceruletide by a marked relaxation with a significant fall in both the infusion and postinfusion pressures. In patients undergoing cholecystectomy for gallstone-associated pancreatitis (n = 8), the sphincter exhibited manometric features of hypotonia with low infusion and postinfusion pressures which were not significantly altered by intravenous ceruletide.

Acute Disease↗

PubMedDate not supplied

Pharmacology, clinical uses, and adverse effects of ceruletide, a cholecystokinetic agent.

Ceruletide, a decapeptide, is a potent cholecystokinetic agent with a direct spasmogenic effect on the gallbladder muscle and bile ducts in humans and animals. It was recently approved by the Food and Drug Administration for use as an adjunct in x-ray examination of the gallbladder and small bowel. The drug causes a coordinated propulsive activity from the duodenum to the ileum and segmenting activity in the colon. Because of this stimulatory effect, ceruletide is useful not only diagnostically as an aid in x-ray examination of the small bowel, but also therapeutically for treatment of postoperative ileus, intestinal atonia, and chronic fecal statis. Because of its pancreatic stimulatory action, it is useful in evaluation of exocrine pancreatic function. In therapeutic doses the adverse effects noted are mild, transient extensions of the drug's pharmacologic actions and are manifest as nausea, vomiting, abdominal pain, and rarely hypotension and tachycardia. On the basis of current evidence, ceruletide is a safe and effective cholecystokinetic agent and small bowel and exocrine pancreatic stimulant.

Animals↗

PubMed1985

Biphasic and long-lasting effect of ceruletide on tardive dyskinesia.

A 55-year-old schizophrenic inpatient with buccolingual dyskinesia was treated with a single dose of ceruletide 0.8 micrograms/kg IM. Time-course effects of the drug were then followed for up to 6 weeks after injection. To assess changes in severity of bucco-lingual dyskinesia objectively, electromyogram (EMG) and microvibration (MV) were recorded. Simultaneously, bucco-lingual dyskinesias were also evaluated by using a five-point rating scale. Before injection of ceruletide, severity of dyskinesia was "moderate" and 3-4 Hz of dyskinetic oral movements were dominant. "Extremely severe" and repetitious gross oral movements (around 1 Hz) were observed within a few minutes after injection and continued for up to 1 h. Thereafter, oral movements tended to decrease, and they disappeared completely 3 weeks after injection. This biphasic and long-lasting effect of ceruletide on tardive dyskinesia might contribute to further understanding of the physio-pathophysiological role of cholecystokinin-like peptides in the brain, and provide a basis for practical treatment of tardive dyskinesia.

Ceruletide↗

PubMed1986

Ceruletide-induced acute pancreatitis in the dog and its amelioration by exogenous secretin.

Large pharmacological doses of ceruletide administered to conscious dogs by intravenous (i.v.) infusion uniformly induce a severe acute necrotizing pancreatitis within 4 h. High-dose i.v. secretin administered for a period of 24 h after cessation of ceruletide infusion resulted in a significant amelioration of the acute pancreatitis compared to non-secretin-treated dogs with acute pancreatitis. Light microscopy of the pancreas in secretin-treated dogs revealed a significant decrease in edema, polymorphonuclear leukocyte infiltration, cell necrosis and acinar cell vacuolization. Serum amylase levels in secretin-treated dogs were significantly decreased compared to non-secretin-treated dogs. The results of this study suggest that high-dose i.v. secretin exerts a beneficial effect on pre-established, ceruletide-induced acute pancreatitis in dogs.

Acute Disease↗

PubMed1990

Acute reduction and long-term improvement of chorea with ceruletide (cholecystokinin analogue).

We studied the effects of ceruletide, a cholecystokinin analogue, on choreic involuntary movement in several neurological diseases by clinical scoring and electromyography in 11 patients. Ceruletide brought about a brief reduction of choreic movement reaching its maximum within 60 min and another long-lasting improvement over several weeks by single administration. The levels of homovanillic acid in cerebrospinal fluid before treatment were significantly higher in cases with long-lasting improvement than those in cases without improvement. We suggest that ceruletide may reduce choreic movement for a long period through effects on the central dopamine system and speculate that such a long-term effect may be accounted for by the change in transmission after the second messengers in neurons.

Adult↗

PubMed1990

Barrel rotation in rats induced by SMS 201-995: suppression by ceruletide.

Intracerebroventricular administration of SMS 201-995 (5 micrograms/rat), a somatostatin analogue, induced barrel rotation in rats. Pretreatment with ceruletide (40 micrograms/100 g b. wt., IP) 3 days or 7 days prior to the injection of SMS 201-995 significantly inhibited the response rate of barrel rotation induced by SMS 201-995, but not that induced by arginine-vasopressin (1 microgram/rat, ICV). The suppressive effect of ceruletide on barrel rotation could be partially countered by MK-329, a selective peripheral CCK (CCK-A) receptor antagonist. Desulfated cerulein did not affect the barrel rotation induced by SMS 201-995. These findings suggest that ceruletide specifically suppresses the barrel rotation evoked by SMS 201-995 in a long-lasting manner possibly acting through CCK-A receptor.

Amino Acid Sequence↗

PubMed1985

Intramuscular ceruletide does not affect food intake in obese and non-obese human subjects.

Intramuscular ceruletide or placebo was given in a randomized double-blind crossover design to 12 non-obese and 12 obese individuals, 30 min before a palatable lunch meal. No significant effects were found on the amount of food intake or the hunger ratings in any group. Although rapid CCK or ceruletide infusions have been found in some studies to reduce food intake in man and animals, slow infusions have increased food intake. Under the present study conditions, the moderate rate of release of ceruletide from intramuscular depots did not affect the food intake.

Adult↗