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PubMed1984

Ceruletide analgesia in biliary colic.

Ceruletide is a decapeptide isolated from the skin of an Australian frog. Its chemical and biologic relationship to cholecystokinin and its potent relaxant effect on the sphincter of Oddi makes it useful in biliary colic. In this double-blind placebo-controlled experiment, 60 subjects with moderate to severe pain caused by biliary colic were injected with ceruletide, 1 ng/kg iv or with an equal volume of saline solution. Pain in the right hypochondrium, referred pain, and Murphy's sign were scored before and after treatment. Data indicate that ceruletide is effective in biliary colic.

Adult↗

PubMed1984

Ceruletide increases dose dependently both jejunal motor activity and threshold and tolerance to experimentally induced pain in healthy man.

The effects of ceruletide on jejunal motility and experimentally induced pain were studied in 16 healthy men, who participated each in four experiments and received in random double blind fashion 5, 10, or 20 micrograms ceruletide intramuscularly or placebo. Jejunal pressures were recorded by three perfused catheters with orifices between 10 and 20 cm aboral of the ligament of Treitz. Ceruletide dose dependently diminished phase I and increased phase II type activity and tended to reduce the number, but not the duration, of activity fronts. The number and amplitude of contractions as well as the area under the curve increased significantly and dose dependently as did threshold and tolerance to electrically and threshold to thermally induced pain. Only mild sedative and other side effects occurred.

Adult↗

PubMed1992

Controlled study of the effect of nicardipine and ceruletide on the sphincter of Oddi.

Although sphincter of Oddi dysfunction is a recognised cause of post cholecystectomy pain, the control mechanisms involved in sphincter of Oddi function are poorly understood. Pharmacological relaxation of the sphincter of Oddi may have a beneficial effect particularly in sphincter of Oddi dysfunction where basal sphincter pressure is high. The aim of this study was to investigate the effects of calcium channel blockade (nicardipine) and synthetic cholecystokinin (ceruletide) on sphincter of Oddi pressures. Nineteen patients (median age 49 years; range 21-75) attending for routine endoscopic retrograde cholangiopancreatographic (ERCP) examination were studied. No patients with evidence of sphincter of Oddi dysfunction were included in the study. Each patient was randomly allocated to receive a three minute intravenous infusion of nicardipine 3 mg (six) ceruletide 5 ng/kg (seven) or placebo (six). Endoscopic biliary manometry was done with recording of basal sphincter of Oddi pressures, sphincter of Oddi phasic wave amplitude and frequency before and after intravenous infusions. In the nicardipine group patients showed a decrease in both basal and phasic amplitude sphincter of Oddi pressure (mm Hg) from the preinfusion values (mean (SEM)) of 24.7 (3.6) and 112.3 (13.4) to 12.9 (2.9) (p less than 0.01) and 89.9 (12.4) (p less than 0.03) after infusion respectively. Ceruletide produced a decrease in sphincter of Oddi phasic wave frequency (c/min) from 3.4 (0.3) before infusion to 2.6 (0.5) after infusion (p less than 0.05). We conclude that nicardipine effectively decreases sphincter of Oddi pressure. This drug may therefore be of value in the treatment of sphincter of Oddi dysfunction where raised sphincter pressures are thought to be the primary pathogenic feature.

Adult↗

PubMed1979

Ceruletide-assisted cholecystography: a clinical assessment.

The cholecystokinetic effect of ceruletide, a synthetic decapeptide similar in action to cholecystokinin, was examined in both a randomized and nonrandomized study in 81 patients scheduled for routine oral cholecystograms. Intramuscular injection of ceruletide in a dose of 0.3 microgram/kg resulted in a mean maximum contraction of the gallbladder of 68% and a mean time until maximum contraction of 28 minutes. Visualization of the cystic duct occurred in 57 patients (70%); the common duct was seen in 67 (83%). Ceruletide demonstrated superior gallbladder contraction when compared to fatty meals and demonstrated no interference with a subsequent upper gastrointestinal series.

Adult↗

PubMed1984

Ceruletide resembles antipsychotics in rats and schizophrenic patients. Preliminary report.

Peptides related to the C-terminal part of cholecystokinin, including ceruletide, were found to be active in a number of behavioral test procedures in rats, predicting antipsychotic action. In a subsequent clinical trial ceruletide was administered intramuscularly in a dose of 40 micrograms twice for 2 consecutive weeks to 6 neuroleptic-treated schizophrenic patients following a single-blind design. In 3 patients, a pronounced long-lasting antipsychotic effect was observed, while in the other 3 the response was less marked. It is suggested that ceruletide may be a potential antipsychotic peptide.

Animals↗

PubMed1990

Effects of ceruletide, administered singly and in combination with central-acting drugs, on discrete shuttle avoidance response in mice.

The single administration of ceruletide at 10-300 micrograms/kg, i.p., slightly but significantly decreased the response rate (frequency of shuttles) under a discrete avoidance task in mice. Over 10 micrograms/kg of ceruletide attenuated the increase in the response rate induced by methamphetamine (0.5 mg/kg, s.c.). However, ceruletide, at 1-300 micrograms/kg, did not significantly enhance the response- and/or avoidance-decreasing effects of chlorpromazine (1 mg/kg, s.c.), haloperidol (0.1 mg/kg, s.c.), pilocarpine (4 mg/kg, s.c.) and N6-(L-2-phenylisopropyl)-adenosine (0.1 mg/kg, s.c.), but rather tended to reduce the avoidance-decreasing effect of chlorpromazine and pilocarpine at 1-100 micrograms/kg.

Animals↗

PubMed1991

Differential antagonism of the stimulant effects of MK-801 and methamphetamine by ceruletide: evaluation by discrete shuttle avoidance response in mice.

A noncompetitive NMDA antagonist MK-801 (0.03-0.3 mg/kg, i.p.) increased the response rate of mice trained under the discrete shuttle avoidance situation to a degree similar to the increase by methamphetamine (0.1-1 mg/kg, i.p.). The cholecystokinin-like decapeptide ceruletide significantly reduced the response-increasing effect of MK-801 (0.1 mg/kg) at 0.001 micrograms/kg; however, only 10 micrograms/kg of ceruletide, which per se inhibited the response, attenuated that of methamphetamine (0.3 mg/kg). The coadministration of MK-801 (0.1 mg/kg) and methamphetamine (0.3 mg/kg) produced no potentiation of the effect, and almost the same effect was maintained even after the additional administration of ceruletide (0.1 microgram/kg).

Animals↗

PubMed1978

Cholecystokinetic cholecystography: efficacy and tolerance studies of ceruletide.

The effect of intravenous and intramuscular administration of ceruletide on gallbladder contraction was investigated in 67 normal volunteers and patients. Of the 45 normal volunteers, 33 received the drug intravenously and 12 intramuscularly in graded ascending doses. By either means of injection, ceruletide produced a substantial contraction of the gallbladder with a measurable reduction in gallbladder area. Based on findings in these groups, the 22 patients requiring oral cholecystography for clinical evaluation received 0.3 microgram/kg intramuscularly. The intramuscular administration of synthetic ceruletide after oral cholecystography, in a dose of 0.o microgram/kg, afforded a safe and effective means of gallbladder contraction, with resultant cystic and common bile duct visualization. Side effects occurred less frequently when the drug was administered intramuscularly and were minimal and self-limiting. Peak contraction (40% or greater reduction in size) occurred as early as 5-15 min after after intramuscular injection and in most instances within 30 min.

Adult↗

PubMed1979

Cholecystokinetic cholecystography: comparison of the effect of intramuscular ceruletide to a fatty meal.

A comparison study of 80 patients using either intramuscular ceruletide or a fatty meal to contract the gallbladder after oral cholecystography is described. The maximum mean percentage reduction of the gallbladder area was significantly greater with ceruletide (59%) compared to a fatty meal (29%). At all time intervals, a 40% or more reduction in gallbladder area occurred in a higher percentage of patients receiving ceruletide, with improvement in cystic and/or common duct visualization occurring at an earlier time than with a fatty meal. There were no adverse effects after gallbladder contraction when large or small calculi were present.

Ceruletide↗

PubMed1980

Ceruletide-assisted examination of the small bowel.

Ceruletide, a decapeptide similar in action to cholecystokinin, was studied in a randomized fashion in 48 patients undergoing routine small bowel examination. Parenteral administration of Ceruletide demonstrated a significantly decreased small bowel transit time (28.8 min) when compared with placebo (67 min) (P less than 0.005). However, this was offset by a diminution in anatomic quality particularly in the distal ileum. A hypotonic action on the duodenual bulb and sweep was observed in 77% of patients after the administration of Ceruletide. This hypotonic effect may prove to be a useful adjunct in the performance of an upper gastrointestinal series.

Adult↗

PubMed1996

Effects of ceruletide and haloperidol on auditory evoked potentials in the cat brain.

The influence of cholecystokinin-like peptide, ceruletide, on EEG and auditory evoked potentials (AEPs) was studied in nine cats. The cats were bearing electrodes implanted in the auditory cortex, hippocampus, reticular formation and cerebellum. Reference drugs used were haloperidol and neostigmine. The hippocampus showed the strongest effect of ceruletide, whereas the cerebellum was virtually unresponsive. The amplitude of AEPs was increased by peptide, an effect lasting up to 21 days which, according to amplitude frequency analysis (AFC) was due to an augmented theta response. The latter possibly indicates increased signal transfer to, or through, the brain structure in question, particularly in the hippocampal neurons. The effects of haloperidol and neostigmine did not reflect those of ceruletide and lasted only a few hours.

Animals↗

PubMed1976

[Effects of ceruletide in the treatment of postoperative paralytic ileus].

After a short analysis of the pathogenetic causes which can lead to paralytic ileus and the drugs at present available for treatment of this serious morbid form, the paper reports results obtained with Ceruletide, a decapeptide which has proved active on intestinal peristalsis in experimental and clinical trials. The results of this study, carried out on 20 patients subjected to surgical operation on the abdomen, treated with Ceruletide by intramuscular route 24-48 hours after the operation, showed that this drug is capable of leading to a quick recovery of intestinal motor activity without causing the patient unpleasant effects for the patient. The practical utility of Ceruletide is evident since by leading to earlier canalisation of the intestine it also allows the venous hydro-electric delivery to be reduced, nasogastric aspiration to be eliminated early and hence the postoperative course to be made more acceptable to the patient.

Ceruletide↗

PubMed1988

In vivo effects of nifedipine and BAY 1 8201 on ceruletide induced gallbladder contraction.

Studies in animals suggest that calcium channel blockers may influence gallbladder contraction. In order to study possible actions in man we examined by ultrasonography the effects of two dihydropyridine derivatives, i.e. nifedipine (20 mg p. o.) and BAY 1 8201 (100 mg p.o.) on ceruletide induced human gallbladder contraction in 9 healthy male volunteers in a randomized, double-blind, three fold crossover study (latin square design). Blood samples for the measurement of plasma drug concentrations were drawn before and at regular intervals up to 8 h after drug ingestion. Ceruletide decreased gallbladder volumes by 52.1 +/- 8.2% (mean +/- 1 SEM) after nifedipine, 53.1 +/- 8.1% after BAY 1 8201 and by 59.3 +/- 10.1% after placebo (NS). Peak plasma concentrations of 53.7 x/: 2.3 ng/ml (geometric mean x/: geometric standard deviation) and of 35.5 x/: 1.5 ng/ml were reached after oral application of nifedipine and BAY 1 8201, respectively. We conclude that human gallbladder contraction in response to ceruletide is not markedly influenced by dihydropyridine derivates in the dosages used in this study. The results reported here stress the importance of calcium released from intracellular stores for the contractility of smooth muscle in the human gallbladder.

Adult↗

PubMed1979

[Conservative treatment of severe paralytic ileus. Clinical experiences with Ceruletid].

After the failure of other medicamentous treatment attempts for paralytic ileus, Ceruletid (Takus) was used in 20 surgical patients. Ceruletid was applied as an infusion of 40 microgram in 250 ml or 500 ml physiological saline solution over a period of 2-3 hours. During this time the occurrence of bowel sounds, flatulence and defecation was observed. The most important clinical and serological parameters were measured before and after treatment. Treatment was successful in 17 cases, in 3 cases no success was achieved. Severe side effects did not occur. The use of Ceruletid in the described form of administration can be recommended for the treatment of paralytic ileus.

Ceruletide↗

PubMed1986

Effect of ceruletide on tardive dyskinesia: a pilot study of quantitative computer analyses on electromyogram and microvibration.

Seven patients with bucco-lingual dyskinesia were treated with a single dose of ceruletide 0.8 micrograms/kg IM, a potent analogue of cholecystokinin octapeptide. Time-course effects of the drug were then followed up to 6 weeks after injection in the longest case. To assess changes in severity of dyskinesia objectively, electromyogram and microvibration were recorded. These data were subjected to the Fast Fourier Transform and an averaged power spectrum was computed. The effect of ceruletide on dyskinesia within 2 h after injection differed (three cases: inhibitory, two cases: facilitatory, two cases: no effect). It was notable that a long-lasting inhibitory effect of this peptide was observed in two severe irreversible cases. The present findings might contribute to further understanding of the physiopathophysiological role of cholecystokinin-like peptides in the brain and to practical treatment of tardive dyskinesia.

Adult↗

PubMed1993

Ceruletide therapy in action tremor following thalamic hemorrhage.

Two men, aged 63 and 71 years, developed a gross action tremor and dysesthesias several months after an intracerebral hemorrhage. CT and MRI showed a small hemorrhage in the posterior region of the lateral nucleus of the thalamus in each patient. The tremor occurred on movement, had frequencies of 2.5-4.5 Hz and the amplitude varied depending on the joint position of the limb. Ceruletide (a cholecystokinin analog) 0.8 micrograms/kg i.m. produced a marked reduction in the action tremor and improved motor function. This effect appeared 10-15 min after the injection, and lasted for up to 4 weeks. It is suggested that ceruletide may be of value in the treatment of action tremors following a thalamic lesion.

Aged↗

PubMed1989

Phospholipase A activities in ascites, serum, lymph, and urine in acute pancreatitis following pancreas stimulation with secretin-ceruletid.

As a result of pancreas stimulation with secretin-ceruletid we were able to measure the release of phospholipase A in ascites, serum, lymph, and urine in acute experimental pancreatitis in the dog. After induction of acute pancreatitis we found no increase over the normal range in serum, lymph, and urine phospholipase A activities. In addition, the stimulation of the exocrine pancreas did not show a significant change in phospholipase A activity. The excessively high phospholipase A activity in ascites following induction of acute pancreatitis fell significantly after pancreas stimulation with secretin-ceruletid.

Acute Disease↗

PubMed1982

Evaluation of intramuscular ceruletide for shortening small bowel transit time.

A double-blind crossover study in 31 normal volunteers showed that intramuscular injection of ceruletide (0.3 microgram/kg) significantly accelerated small bowel transit of barium when compared to placebo. The only adverse effect was frequent pain at the injection site. There was a significant degradation in the quality of small bowel coating and distension in only 10% of the volunteers. Despite these problems, intramuscular administration of ceruletide may become a useful method for decreasing the prolonged time required for most small bowel examinations.

Adult↗