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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Antistereotype effects of ceruletide and some neuroleptics differentiated by interactions with clonazepam, muscimol, scopolamine and clonidine. 287 54

The decapeptide from the frog Hyla caerulea, caerulein (caerulein diethylammonium hydrate, ceruletide, CER) is chemically closely related to the C-terminal octapeptide of cholecystokinin (CCK-8). Like CCK-8, CER and some of its analogues produce many behavioural effects in mammals: inhibition of intake of food and water; antinociception; sedation; catalepsy; ptosis, antistereotypic, anticonvulsive and tremorolytic effects; inhibition of self-stimulation. Effects of CER in man comprise sedation, satiety, changes in mood, analgesia and antipsychotic effects. A modulation of central dopaminergic functions appears to be one possible mechanism of CER and its analogues. A common denominator for all effects of CER is, at present, not evident.
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PMID:Caerulein and its analogues: neuropharmacological properties. 391 10

The central depressant effects of ceruletide (CER, 0.04 mg/kg s.c.) and cholecystokinin octapeptide (CCK-8, 0.25 mg/kg s.c.) were compared with those of clonidine (0.04 mg/kg s.c.). At doses that were nearly equipotent with respect to motor inhibition (catalepsy, reduction in ambulation and exploratory rearing), only the peptides produced ptosis. Yohimbine (1 mg/kg s.c., 30 min) antagonized the effect of clonidine but not of the peptides. Clonidine (0.07-0.2 mg/kg s.c., 30 min) antagonised the ptotic action of the peptides, and this effect was abolished by yohimbine (0.2-1 mg/kg i.p.) but resistant to haloperidol (0.05 and 0.15 mg/kg i.p.). These results separate the behavioural effects of the peptides from those of clonidine and also the ptotic effect of the peptides from their effect on motor activity. The antiptotic effect of clonidine may originate from activated adrenergic autoreceptors.
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PMID:Clonidine and yohimbine separate the sedation and the ptosis caused by cholecystokinin octapeptide and ceruletide. 609 Jan 62

Haloperidol in low doses antagonized the apomorphine-induced cage-climbing behaviour of mice, whereas ceruletide (CER) and its analogue, Nle8-CER-(4-10) had very weak anticlimbing efficacy; Nle8-CER and diazepam were inactive. The ptosis caused by CER and cholecystokinin octapeptide (CCK-8) was antagonized by apomorphine in doses 27 times smaller than those effective against the haloperidol-induced ptosis. No such differences occurred when either methylphenidate or picrotoxin replaced apomorphine. Low-dose haloperidol was an antagonist to the antiptotic effect of apomorphine versus both CER and CCK-8. The rearing inhibiting effect of CER and haloperidol, in contrast to that of clonazepam, was very resistant to apomorphine. Methylphenidate was weakly effective against clonazepam and haloperidol but inactive versus CER. Picrotoxin was no antagonist to either rearing inhibiting agent. The results taken together suggest presynaptic sites of the dopaminergic system as important for the production of ptosis by CCK-like peptides.
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PMID:Neuroleptic-like effects of ceruletide and cholecystokinin octapeptide: interactions with apomorphine, methylphenidate and picrotoxin. 614 Jan 74

Cholecystokinin octapeptide (CCK-8), caerulein and diazepam inhibited exploratory rearing activity and harman-induced convulsions in mice. Pretreatment with the selective benzodiazepine receptor antagonist Ro 15-1788, reduced or abolished the sedative and anticonvulsive effects of diazepam, but left the same effects of both peptides unaffected. The peptide-induced ptosis was even increased by Ro 15-1788. The results suggest that the CCK-like peptides do not directly interact with the benzodiazepine receptor.
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PMID:Caerulein and cholecystokinin octapeptide (CCK-8): sedative and anticonvulsive effects in mice unaffected by the benzodiazepine antagonist Ro 15-1788. 628 94

Ten ceruletide analogues and cholecystokinin octapeptide (CCK-8) were compared with ceruletide regarding neuropharmacological effects in mice after peripheral administration. The effects under study were inhibition of motor response to noxious stimulation (hot plate), production of ptosis, inhibition of exploratory rearing activity, elevation of threshold for picrotoxin-induced convulsions, and antagonism of methylphenidate-induced gnawing. Desulfation, deamidation and shortening of the peptide chain by five amino acids destroyed all pharmacological activities of ceruletide. Other modifications were of unequal consequences for the pharmacological profile of a given analogue, decreasing some effects while increasing others. Hence, structural changes of the ceruletide molecule resulted in modulations of both potency and selectivity.
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PMID:Central effects of ceruletide analogues. 628 99

The general pharmacological properties of a novel cholecystokinin-A antagonist, loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-pentylgl utaramic acid, CR 1505, CAS 107097-80-3) on central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems were investigated in experimental animals. 1. Central nervous system: At a dose of 30 mg/kg, i.v. loxiglumide showed ptosis in one of 6 mice, but at doses of 3 and 10 mg/kg, i.v. no change on gross behavior in mice. Loxiglumide had no effect on locomotor activity and thiopental-induced hypnosis, anti-convulsive activity, analgesic activity in mice and rectal temperature changes in rats. 2. Autonomic nervous system: In vitro, loxiglumide at concentrations of 10(-4) and 3 x 10(-4) mol/l slightly inhibited agonist-induced contractions in the isolated guinea pig ileum and spontaneous rhythmic contractions in the isolated non-pregnant rat uterus. But loxiglumide had no effect on oxytocin-induced contraction in isolated non-pregnant rat uterus. 3. Cardio-respiratory system: Loxiglumide had no effect on heart rate and electrocardiogram in anesthetized dogs. But it slightly increased blood pressure and decreased the frequency of respirations at a dose of 30 mg/kg, i.v. Furthermore, loxiglumide slightly decreased femoral arterial blood flow at doses of more than 3 mg/kg, i.v. On the other hand, it had no effect on contractile force or contraction rate in the isolated guinea pig atrium and resting tension in the isolated rabbit aorta. 4. Gastrointestinal system: Loxiglumide increased bile secretion at doses of 10 and 30 mg/kg, i.v. in anesthetized rats and at doses of 3, 10 and 30 mg/kg, i.v. in anesthetized dogs. However, total bile acid output was not affected by loxiglumide. On the other hand, loxiglumide had no effect on pancreatic secretion, gastric secretion and gastric emptying in rats and intestinal transport activity in mice. 5. Hematology: In vitro, in the case of samples without bovine serum albumin, at concentrations of more than 1.9 x 10(-3) mol/l loxiglumide showed hemolysis, while in the case of samples with bovine serum albumin, at concentrations of more than 6.9 x 10(-3) mol/l loxiglumide showed hemolysis, and its maximal potency was weak compared to albumin-free conditions. On the other hand, in vivo, loxiglumide had no effect on hemolysis. In addition, it had no effect on platelet aggregation, prothrombin time and activated partial thromboplastin time. 6. Miscellaneous pharmacological actions: Loxiglumide had no effect on local anesthetic activity in guinea pigs and renal function in mice. These results suggest that loxiglumide seems to produce no serious side effects on the central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems at pharmacologically effective doses.
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PMID:General pharmacological profile of the novel cholecystokinin-A antagonist loxiglumide. 945 Jan 67