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PubMed1988

Effects of ceruletide on clinical symptoms and EEGS in schizophrenia.

1. The efficacy of ceruletide as a supplement in treating schizophrenics was tested by monitoring the Brief Psychiatric Rating Scale (BPRS) and the EEG. 2. Eight male inpatients with schizophrenia were administered fixed doses of neuroleptics during the study. 3. A control EEG recording and BPRS scoring were done before ceruletide administration. 4. Doses of 0.8 micrograms/kg/week of ceruletide and of placebo were given intramuscularly in a double-blind, crossover design for 3 consecutive weeks, and no treatment followed for 1 week. 5. EEG recordings and BPRS scoring were carried out once weekly. There were no significant differences in the total BPRS scores or the scores of each item between ceruletide and placebo. 6. With ceruletide treatment, the power values of the frontal EEGs increased in the whole bands but only in the first week. 7. The EEG values in the occipital area increased in alpha and beta activities slightly in the third week and markedly in the fourth week. 8. The power values in the right temporal area decreased in fast beta activity in the second and third weeks but increased in alpha activity in the third and fourth week. 9. The power of the left temporal area increased in both alpha and beta bands in the second week, and this continued to the fourth week. 10. These results suggest that treatment with ceruletide might fail to improve the symptoms of schizophrenics but does affect their EEGs, and that ceruletide may have a delayed effect.

Adult↗

PubMed1986

A comparative study on the antipsychotic properties of desenkephalin-gamma-endorphin and ceruletide in schizophrenic patients.

The neuropeptides desenkephalin-gamma-endorphin (DE gamma E) and ceruletide were administered intramuscularly to patients with schizophrenic psychoses following a double-blind placebo-controlled design, including a total of 44 subjects. Neuroleptic medication was continued during the experimental period, which was started with one placebo injection for all patients. One week later subjects received a single intramuscular injection with 3 mg DE gamma E, 40 micrograms ceruletide or placebo. After an interval of 10 days, the patients received six similar injections over a period of 2 weeks. Treatment with either peptides resulted in a decrease of psychotic symptomatology as compared to placebo treatment. The beneficial effect of the peptides lasted at least 2 weeks after the experimental treatment period. Of the 14 patients treated with placebo only, three showed a slight response. Of the 30 patients treated with the neuropeptides, eight did not respond (DE gamma E: 3; ceruletide: 5), eight had a slight response (DE gamma E: 6; ceruletide: 2) and 14 responded moderately or markedly (DE gamma E: 6; ceruletide: 8). No obvious difference between the effects of the two neuropeptides was found, besides a somewhat earlier onset of the effect of ceruletide. Patients presenting relatively less negative psychotic symptoms were particularly susceptible to treatment with either peptide. Apart from slight and short-lasting gastrointestinal complaints after the first injections with ceruletide in some patients, no side effects were observed.

Adult↗

PubMed1989

[Neurotrophic effect of ceruletide and LH-RH on ventral spinal cord in culture].

This experiment was undertaken in order to study the probable trophic effect of ceruletide and LH-RH on cultured ventral spinal cord. The ventral spinal cord from 13-14-gestational day rat embryos were explanted, following a conventional culturing method. Explants in the culture medium were fed ceruletide and LH-RH at different concentrations. An equal volume of PBS was administered to the control explants. For quantitative analysis of the trophic effect of ceruletide and LH-RH, a numerical score from 0 to 4 was determined at the 7th culture day, based on the length and extension of neurite growth estimated. The presence of ceruletide, the neuritic extension of ventral spinal cord exceeds control values 3.5-6.3 times. The growth zone of the spinal cord explants increases in the ceruletide treated culture, LH-RH treated culture, on the other hand, had no promoting effect on neurite growth. The possible mechanism of trophic effect of ceruletide on cultured ventral spinal cord was briefly discussed. These experimental observation have important implications regarding to potential therapeutic effects of ceruletide n amyotrophic lateral sclerosis.

Animals↗

PubMed1985

Ceruletide for schizophrenia: a double-blind study.

Ceruletide, an analog of cholecystokinin (CCK), has been reported to have neuroleptic-like activity in mice, and, in three open studies, to benefit schizophrenic patients. This study evaluated ceruletide in schizophrenia using a double-blind design. Subjects were 17 chronic schizophrenics with residual symptoms following stabilization with neuroleptics. Patients randomly received two injections, 1 week apart, of either ceruletide (0.6 microgram/kg im) or placebo, while continuing neuroleptics; this regimen was found helpful in earlier studies. Evaluation included ratings of 29 variables related to prognosis in schizophrenia (e.g., age, number of previous hospitalizations), regular BPRSs and SCL-90s, and psychiatrist, patient, and relative ratings of global improvement. Results showed few significant differences between ceruletide and placebo, with exceptions as likely to favor placebo as ceruletide. Among the patients on ceruletide, no predictors of benefit were found. Possible reasons for the negative results are discussed.

Antipsychotic Agents↗

PubMed1984

Effect of cholecystokinin octapeptide and ceruletide on release of acetylcholine from cerebral cortex of the rat in vivo.

The effect of cholecystokinin octapeptide (CCK-8) and its analogue, ceruletide on release of acetylcholine (ACh) from the cerebral cortex was investigated in urethane-anaesthetized and in unanaesthetized rats. Cholecystokinin octapeptide and ceruletide markedly stimulated output of ACh at doses of 1.5 and 5.0 micrograms/kg (i.p.), respectively. This effect was prevented by proglumide (160 mg/kg i.p.), a specific cholecystokinin receptor antagonist. At doses of 10 micrograms/kg (i.p.) and more, both CCK-8 and ceruletide decreased output of ACh from the cerebral cortex. The decrease was prevented by naloxone (1 mg/kg, s.c.), and replaced by a short-lasting increase. Cholecystokinin octapeptide and ceruletide appear therefore to affect the activity of cortical cholinergic fibres by acting upon both specific and opiate receptors. The interaction between CCK-8 and ceruletide, and opiate receptors either direct or through the release of endogenous opiates, was also demonstrated by the antagonism between ceruletide (1, 5 and 10 micrograms/kg, i.p.) and analgesia induced by morphine (5 mg/kg, s.c.), evaluated by the tail-flick test in the rat.

Acetylcholine↗

PubMed1985

Analgesic effect of ceruletide compared with pentazocine in biliary and renal colic: a prospective, controlled, double-blind study.

The analgesic effect of ceruletide in biliary and renal colic was evaluated by a randomized, double-blind study in 82 patients. Ceruletide was compared with pentazocine, a well-established analgetic agent. Rapid and effective analgesia was obtained by intramuscular injection of ceruletide 0.5 micrograms/kg in 56 patients with biliary colic. The analgesic effect of ceruletide compared well with pentazocine 0.5 mg/kg im, and was associated with remarkably fewer side effects. In 26 patients with renal colic, ceruletide was significantly inferior to pentazocine. These data support the recommendation of ceruletide as a first-choice analgetic agent for biliary colic.

Adult↗

PubMed1985

Ceruletide intravenous dose-response study by a simplified scintigraphic technique.

The intravenous dose response of a ceruletide diethylamine (ceruletide) was established by a simplified scintigraphic technique where multiple graded doses were given sequentially on a single occasion. The gallbladder volume was represented nongeometrically by 99mTc-IDA counts. The mean latent period, ejection period, and ejection rate were similar for all four groups of subjects given 1-20 ng/kg of ceruletide. The mean (+/- SD) ejection fractions after 1, 5, 10, and 15 ng/kg of ceruletide as the single dose were 19.4 +/- 11.9%, 59.6 +/- 26.0%, 55.2 +/- 23.3%, and 67.8 +/- 8.7%, respectively. These ejection fractions were similar to the values when the identical dose of ceruletide was administered sequentially either before or after another dose. A dose of 5 ng/kg produced the most physiologic type of emptying. Intravenous doses of 10 ng/kg and larger caused adverse reactions in 42% of the total doses in the form of abdominal pain, nausea, systolic and diastolic hypotension, or bradycardia. It is concluded that the dose response of a cholecystokininlike agent (ceruletide) can be established reliably by a scintigraphic technique where multiple graded doses are given on a single occasion.

Adult↗

PubMed1995

Contrasting effects on methamphetamine sensitization of ceruletide, a cholecystokinin-like decapeptide, and haloperidol.

Ceruletide, a cholecystokinin-like decapeptide, and haloperidol show neuroleptic actions through inhibition of dopamine release and blockade of dopamine receptors, respectively. In this study, the effects of both drugs on methamphetamine sensitization were assessed by means of ambulation in mice. The enhancement in ambulation increase caused by five repeated administrations of methamphetamine (2 mg/kg, SC) at 3- to 4-day intervals was dose-dependently reduced when it was administered simultaneously with ceruletide (0.01-0.1 mg/kg, SC) or haloperidol (0.03-0.3 mg/kg, SC). However, only haloperidol could inhibit the induction of methamphetamine sensitization as assessed by challenge with methamphetamine alone. Post-treatment with ceruletide (0.03 mg/kg) 3 h after each methamphetamine accelerated, whereas such post-treatment with ceruletide (0.1 mg/kg) or haloperidol (0.03-0.3 mg/kg) delayed, the induction of methamphetamine sensitization. On the other hand, mice given five pretreatments with ceruletide (0.01-0.1 mg/kg) or haloperidol (0.03-0.3 mg/kg) at 3- to 4-day intervals did not exhibit any significant change in the sensitivity to methamphetamine. The present results suggest that, in contrast to the dose-dependent inhibition of methamphetamine sensitization in the simultaneous administration and post-treatment schedules, although both drugs can antagonize the acute stimulant effect of methamphetamine.

Animals↗

PubMed1986

Antistereotype effects of ceruletide and some neuroleptics differentiated by interactions with clonazepam, muscimol, scopolamine and clonidine.

Compulsive gnawing was produced in mice by administration of either methylphenidate or (after sensitizing pretreatment with the neuroleptic, tetflutixol) apomorphine. Drugs which antagonise stereotypy, such as ceruletide (CER, a sulphated decapeptide related to cholecystokinin octapeptide), haloperidol, zuclopenthixol and fluphenazine were applied in equipotent doses (reducing stereotypy by 80%). Clonazepam, muscimol, clonidine and scopolamine (but not methylscopolamine) antagonized to a different extent the antistereotype effect of ceruletide and the neuroleptics. The ED50s for clonazepam and other drugs, were determined; clonazepam had the greatest potency. Regarding the antagonism of the antistereotype effect, ceruletide was similar to but by no means congruent with haloperidol. The antagonism of the antistereotype effect was specific because other effects of ceruletide and cholecystokinin octapeptide (inhibition of exploratory rearing activity, ptosis, antinociception, hypothermia) were not antagonized by clonazepam and only weakly modified by scopolamine. Methylscopolamine was ineffective throughout, indicating a central site for the mechanism of the actions studied of scopolamine. In conclusion, the antistereotype effect of ceruletide is different from that of conventional neuroleptic drugs and functionally independent of other behavioural effects of the cholecystokinin-like peptides.

Animals↗

PubMed1986

A double-blind study with ceruletide in chronic schizophrenic patients: biochemical and clinical results.

We evaluated ceruletide, a cholecystokininlike peptide, in a double-blind, placebo-controlled study of 20 male chronic schizophrenic patients. After baseline investigations, 10 patients received 0.3 microgram/kg body weight ceruletide, and 10 patients received placebo (normal saline) intramuscularly once weekly for 3 consecutive weeks. Psychopathology was rated on the Brief Psychiatric Rating Scale and the Nurses' Observation Scale for Inpatient Evaluation. Blood was drawn on the same days for estimation of norepinephrine, epinephrine, beta-endorphin, cortisol, and prolactin. There were no significant changes in biochemical parameters. With regard to psychopathology, no significant differences in behavioral ratings were found between the ceruletide- and placebo-treated groups. Furthermore, there was no changes in either positive or negative symptoms of schizophrenia secondary to ceruletide. Contrary to uncontrolled studies, we failed to show antipsychotic properties of ceruletide.

Adult↗

PubMed1992

Treatment of tardive dyskinesia with ceruletide: a double-blind, placebo-controlled study.

The effectiveness of a once-weekly i.m. injection of ceruletide (0.8 microgram/kg) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia (TD) was evaluated in a double-blind, placebo-controlled, matched-pairs study. Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo. Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow, but long-lasting improvement of TD symptoms. Side effects, which were mild and transient, consisted mainly of nausea and epigastric discomfort. The incidence of side effects did not differ between the ceruletide- and placebo-treated groups. Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia.

Adult↗

PubMedDate not supplied

Ceruletide decreases food intake in non-obese man.

Cholecystokinin decreases food intake in animals and in man. This study investigated whether the structurally related ceruletide reduces food intake in healthy non-obese man. Twelve females and 12 males participated, after an over-night fast, in each of two experiments. During the basal 40 min, saline was infused IV. Thereafter, the infusion was, in random double blind fashion, either continued with saline or switched to 60 or 120 ng/kg b. wt/hr ceruletide. Butter was melted in a pan and scrambled eggs with ham were prepared in front of the subjects, who were instructed to eat, together with bread and mallow tea, as much as they wanted. With 120 ng/kg/hr ceruletide, the subjects ate significantly less (16.8 percent) than with saline (3725 kJ +/- 489 SEM and 4340 kJ +/- 536, respectively; p less than 0.025). They also reported less hunger (p less than 0.005) and activation (p less than 0.005) and activation (p less than 0.01), and had longer reaction times (p less than 0.01) and a weaker psychomotor performance (p less than 0.025). 60 ng/kg/hr ceruletide decreased food intake only slightly (6.6%; 3089 kJ +/- 253 and 3292 kJ +/- 300 respectively) and no significant changes in the above measures occurred. In conclusion, ceruletide reduces food intake in man, thus resembling the effects of cholecystokinin.

Adult↗

PubMed1988

The effect of ceruletide on tardive dyskinesia: a double-blind placebo-controlled study.

1. In a double-blind placebo-controlled study of 37 patients with tardive dyskinesia, the therapeutic effect of ceruletide was evaluated. 2. The patients were assigned at random to two groups that received either intramuscular injections of 0.8 micrograms/kg of ceruletide or placebo once weekly for 4 weeks. Conventional neuroleptic medication was not changed 3 weeks prior to and throughout the study period. Tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale over an 8-week period. 3. Ceruletide had a more pronounced effect on TD than the placebo however, because of the limited number of subjects examined, the difference between the two groups was not significant. Ceruletide was more effective than placebo in patients under 60 years of age (p less than 0.05) and whose antipsychotic medication was mainly butyrophenones. 4. No serious side effect was noted. 5. The findings suggested that ceruletide therapeutically benefits patients with tardive dyskinesia.

Ceruletide↗

PubMed1992

Late onset and long-lasting suppressive effects of ceruletide, an analogue of cholecystokinin, on c-fos mRNA expression in the rat striatum.

C-fos mRNA expression by stimulation with subcutaneous (s.c.) administration of saline or cycloheximide (CHX) was examined in the rat striatum with or without pretreatment with ceruletide, an analogue of cholecystokinin. The c-fos mRNA induction 1 h after CHX stimulation (25 mg/kg, s.c.) was significantly suppressed by ceruletide pretreatment (80 micrograms/kg, s.c.) 2 h before CHX stimulation in the striatum, and tended to be suppressed by ceruletide pretreatment 4 h before saline or CHX stimulation. Long-lasting and inhibitory effects of ceruletide on dyskinesia and on dopaminergic (DAergic) neuronal systems, and c-fos mRNA expression by activation of the DAergic system have been reported. The present findings together with previous reports suggest that ceruletide might have late onset and long-lasting suppressive effects on the expression of c-fos mRNA in the striatum and that these effects might be related to its effects on DAergic neuronal transmission.

Animals↗

PubMed1998

Ceruletide inhibits phencyclidine-induced dopamine and serotonin release in rat prefrontal cortex.

Phencyclidine (PCP; 5.0 mg/kg, i.p.) produced a greater increase in extracellular dopamine (DA) levels in the prefrontal cortex than in the striatum, while PCP increased the extracellular 5-hydroxytryptamine (serotonin; 5-HT) levels in the prefrontal cortex but not the striatum, as determined by in vivo microdialysis in awake, freely moving rats. The cholecystokinin (CCK)-related decapeptide ceruletide (120 and 400 microg/kg, i.p.), administered 60 min prior to PCP, significantly attenuated the PCP-induced increase in the extracellular levels of DA and 5-HT in the prefrontal cortex, but not in the striatum. These effects were reversed by PD 135,158, a selective CCK-B receptor antagonist (0.1 mg/kg, s.c.), administered 5 min prior to ceruletide. When administered alone, ceruletide (400 microg/kg, i.p.) significantly increased basal extracellular DA levels only in the prefrontal cortex. The selective N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (0.5 mg/kg, i.p.) also increased extracellular DA levels in the prefrontal cortex, but this effect was unaffected by ceruletide pretreatment. These results suggest that ceruletide may differentially modulate basal and PCP-induced release of DA and 5-HT in the prefrontal cortex.

Animals↗

PubMedDate not supplied

Effect of ceruletide on discriminated avoidance behavior in rats.

To clarify the central action of peripherally administered ceruletide, we examined the effects of ceruletide and four different classes of neuroleptics, i.e. haloperidol, chlorpromazine, oxypertine and sulpiride, on the discriminated avoidance response (DAR) in rats. Ceruletide and sulpiride did not suppress the DAR over a broad range of doses, whereas other three neuroleptics caused a dose-related decrease in both avoidance and response rates. In addition, the combined administration of ceruletide (100 micrograms/kg s.c.) and neuroleptics at critical doses that suppress the DAR caused a significant reduction in the avoidance rate without affecting the response rate, compared with neuroleptics alone. These findings suggest that ceruletide influences the central dopaminergic system, potentiating the central effects of neuroleptics and producing the favorable therapeutic effects observed in the clinical trials.

Animals↗

PubMed1979

[Improvement of oral cholecystography and cholangiography with ceruletid (author's transl)].

Following oral cholecystography in 100 patients, the conventional "fatty meal" was replaced by an intramuscular injection of Ceruletid in a dose of 0.4 microgram/kg body weight. The synthetic decapetide Ceruletid is a substance with a hormone-like effect on the gastro-intestinal tract. It contracts smooth muscle in the gut and stimulates secretion in the stomach and the exocrine pancreas. Compared with other substances producing contraction which are given orally, Ceruletid acts more quickly and more powerfully in producing contraction of the gall bladder muscle. In 86% of positive cholecystograms, this resulted in satisfactory demonstration of the bile duct, 66% better than for oral substances. Many abnormalities, particularly localised adenomyomatosis, can only be diagnosed after good contraction of the gall bladder. Side effects, such as nausea, dizziness and a feeling of heat were transitory. In three patients it led to vomiting. The rapid and certain effect of Ceruletid during oral cholecystography requires reassessment of the role of intravenous cholangiography in diagnosis. Particularly amongst out-patients, with a high proportion of normal gall bladders, it is possible to complete the examination in one stage by demonstrating the bile duct with Ceruletid.

Bile Ducts↗

PubMed1988

Pharmacological manipulation of adynamic ileus: controlled randomized double-blind study of ceruletide on intestinal motor activity after elective abdominal surgery.

In a double-blind placebo-controlled trial of patients undergoing elective abdominal surgery (n = 91), a single intravenous infusion of ceruletide (2.5 ng kg-1 min-1 for 1 hour) resulted in audible bowel sounds in 42/47 patients as opposed to 30/44 receiving placebo (P less than 0.025). Excessive bowel sounds were noted in 16 patients in the ceruletide group and four receiving placebo (P less than 0.01). Significantly more patients (P less than 0.01) in the ceruletide group (22/45 versus 9/44) passed flatus per rectum between the second and third post-operative day. Ceruletide infusion was accompanied by a significant increase in the incidence of nausea and vomiting (P less than 0.005, P less than 0.0025) but these side effects were short-lived. These results indicate that ceruletide is likely to be a useful therapeutic agent for acute intestinal adynamic motility disorders.

Abdomen↗