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Biomedical subjects

G Zetler

Publications and source records attributed to G Zetler.

At least 37 records · Page 2Linked to original sources
PubMed1983

Cholecystokinin octapeptide (CCK-8), ceruletide and analogues of ceruletide: effects on tremors induced by oxotremorine, harmine and ibogaine. A comparison with prolyl-leucylglycine amide (MIF), anti-Parkinsonian drugs and clonazepam.

Cholecystokinin octapeptide (CCK-8), ceruletide (caerulein, CER) and 10 analogues of ceruletide, were studied in mice for antagonism of the tremors induced by harmine (5 mg/kg, s.c.), ibogaine (20 mg/kg, s.c.) and oxotremorine (0.2 mg/kg, s.c.). The following reference drugs were tested for comparison: prolyl-leucylglycine amide (MIF), atropine, haloperidol, biperiden, ethopropazine, trihexyphenidyl, methixene and clonazepam. All treatments were subcutaneous, the antagonists being given 10 min (in some trials 30 min) before the tremorogen. Tremorolytic potency (ED50) was calculated from dose-response curves. Against the tremors induced by either harmine or ibogaine, CCK-8 and ceruletide, as well as many of the analogues of ceruletide had greater tremorolytic potency than the reference drugs. Against oxotremorine, however, ceruletide and its most potent analogue, Nle8-CER (other analogues were not tested) were inactive and MIF showed very little effectiveness. Additional experiments on hypothermia and sedation as well as evaluation of previous studies on other central actions suggested that the tremorolytic effect of CCK-like peptides is independent of other central effects. The CCK-like peptides may play a physiological role in the regulation of extrapyramidal motor activity.

Alkaloids↗
PubMed1982

Caerulein and cholecystokinin octapeptide (CCK-8): sedative and anticonvulsive effects in mice unaffected by the benzodiazepine antagonist Ro 15-1788.

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.

Animals↗
PubMed1982

Caerulein and morphine in a model of visceral pain. Effects on the hypotensive response to renal pelvis distension in the rat.

In pentobarbital-anaesthetized rats (60 mg/kg, i.p.) renal pelvis distension with a pressure of 80 cm H2O caused a decline in mean arterial blood pressure. This pressure response, which disappeared rapidly after cessation of the distension, was used to study the effects of analgesic drugs known to be effective in renal colic pain in man. Morphine (0.75 and 1 mg/kg, s.c.) and the decapeptide caerulein (1.6, 4 and 8 microgram/kg, s.c.) abolished the pressure response. The effects of the largest doses lasted for at least 30 min. Ineffective in this respect were (a) desulphated caerulein (40 microgram/kg, s.c.) and (b) additional doses of pentobarbital (20 and 40 mg/kg, s.c.). This shows (a) the importance of the sulphated tyrosine (known from previous studies on central effects) and (b) the missing influence of the depth of anaesthesia. Naloxone (0.5 mg/kg, s.c.) abolished the effect of morphine (1 mg/kg, s.c.) but failed to influence that of caerulein (8 microgram/kg, s.c.). Even a fourfold dose of naloxone (2 mg/kg, s.c.) did not weaken the effect of caerulein. Naloxone, per se, was ineffective. These results suggest different mechanisms of the present effects of morphine and caerulein. It appears that renal pelvis distension in the anaesthetized rat can serve as a model of renal colic.

Animals↗
PubMed1982

Cholecystokinin octapeptide, caerulein and caerulein analogues: effects on thermoregulation in the mouse.

Cholecystokinin octapeptide (CCK-8), caerulein and seven out of ten analogues of caerulein produced in mice, after subcutaneous administration, a dose-dependent drop in rectal temperature. For the hypothermic effect, i.e. a decrease in temperature by at least 1.5 degree C, ED50's were estimated with these peptides and with morphine, haloperidol and chlorpromazine. Caerulein was most potent, having an ED50 of 4.6 nmol/kg. With the aid of naloxone, atropine, phenytoin and desipramine the hypothermic effect of caerulein could be separated from that of morphine and haloperidol. These experiments, together with those on the relationship between chemical structure and effect, led to the conclusion that the thermoregulatory action of CCK-like peptides may be independent from other central actions, and vice versa.

Animals↗
PubMed1982

Caerulein and morphine: an attempt to differentiate their antinociceptive effects.

The antinociceptive effect in mice (hot-plate test) of caerulein (0.15 mg/kg s.c.) was many times more resistant to naloxone than that of morphine (2 mg/kg s.c., equipotent with the caerulein dose). The ED50 (mg/kg s.c.) of naloxone (given simultaneously with an agonist) was with morphine 0.01 and with caerulein 0.07. When administered intravenously after the agonist, the ED50 (mg/kg i.v.) against morphine was 0.012 and that against caerulein was 0.62. In either type of experiment the dose-response lines of naloxone against caerulein were very shallow as compared with those against morphine. A caerulein dose of 5 micrograms/kg enhanced the antinociceptive effect of morphine only when given before morphine, but not when given after it. The limited additivity of the effects together with the different susceptibility to naloxone of the antinociceptive actions indirectly suggest that caerulein and morphine do not share the same mechanism of action. Palpebral ptosis occurred only after caerulein and was completely resistant to naloxone 8 mg/kg s.c.

Analgesics↗
PubMed1981

Anticonvulsant effects of caerulein, cholecystokinin octapeptide (CCK-8) and diazepam against seizures produced in mice by harman, thiosemicarbazide and isoniazid.

Caerulein, cholecystokinin octapeptide (CCK-8) and diazepam delayed the onset of seizures produced by harman and thiosemicarbazide (TSC). Caerulein had the potency of diazepam, whereas CCK-8 was less active by a factor of four. The convulsions induced by isoniazid (INH) were very resistant to both caerulein and diazepam; CCK-8 was not tested against isoniazid. Haloperidol did not influence the effect of TSC; it enhanced isoniazid-induced seizures, and antagonized the convulsant effect of harman.

Animals↗
PubMed1981

Interactions of caerulein and morphine on gastrointestinal propulsion in the mouse.

The effects of subcutaneously administered caerulein (ceruletide) and morphine hydrochloride on gastric emptying and gastrointestinal propulsion were studied in male mice. Drug effects were evaluated by the movement of Indian ink administered directly into the stomach after drug injection. Morphine inhibited both gastrointestinal propulsion ( ED50 = 2.1 mumol/kg) and gastric emptying (ED50 - 43 mumol/kg). Caerulein enhanced gastrointestinal propulsion (ED50 = 0.93 nmol/kg) but inhibited gastric emptying (ED50 = 17 nmol/kg). Inhibition of gastric emptying was further potentiated by the combined administration of caerulein and morphine. Naloxone reversed both effects of morphine but not those of caerulein. Morphine antagonized the propulsion-enhancing effect of caerulein.

Animals↗
PubMed1981

Central effects of ceruletide analogues.

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.

Analgesia↗
PubMed1981

Pharmacokinetics and organ distribution of methotrexate in the rat.

After intravenous injection of 31 mg/kg methotrexate (MTX), its concentrations were determined in plasma, liver, kidney, bone marrow, stomach, duodenum, jejunum, colon and muscle up to 23 days, using an enzymatic assay. Plasma pharmacokinetics were described by a triexponential function, with a terminal half-life of 4.2 h. Up to 1.5 h after injection, the initial rapid decline of MTX concentrations in bone marrow, kidney, and liver roughly paralleled that in plasma. The terminal half-life of MTX in bone marrow was greatly prolonged (37 h), while MTX remained nearly constant in liver (0.57 microgram/ml) and kidney (0.53 microgram/ml) from 6 h to 23 days. In the intestines, luminal as well as tissue MTX concentrations were determined. The stomach showed a triexponential decay of tissue MTX and low luminal concentrations throughout. In the duodenum, the middle of jejunum, and the colon tissue MTX seemed to follow a bi- or triexponential function. However, high luminal concentrations due to MTX biliary excretion, when reaching a given intestinal portion, increased the MTX tissue concentration in this segment.

Animals↗
PubMed1980

Effects of cholecystokinin-like peptides on rearing activity and hexobarbital-induced sleep.

Caerulein and the C-terminal octapeptide of cholecystokinin (CCK-8), when subcutaneously injected into mice, inhibited spontaneous rearing activity and prolonged the hexobarbotal sleeping time. These effects were resistant to naloxone. In molar terms, caerulein was 40 times (hexobarbital potentiation) or 115 times (rearing) more potent than diazepam. CCK-8 was less active than caerulein) though still superior to diazepam.

Animals↗
PubMed1980

Anticonvulsant effects of careulein and cholecystokinin octapeptide, compared with those of diazepam.

Caerulein and the C-terminal octapeptide of cholecystokinin (CCK-8), after subcutaneous administration to mice, both delayed the onset and retarded the development of toxic effects of convulsants such as strychnine, pentetrazol, bicuculline, and picrotoxin. They also increased the seizure threshold doses of intravenously infused pentetrazol and picrotoxin. In this regard, both peptides were at least equipotent with diazepam.

Animals↗
PubMed1980

Field-stimulus response of guinea-pig atria as influenced by the peptides angiotensin, bradykinin, and substance P.

Field stimulation produced in isolated guinea-pig left atria a positive inotropic response, which was highly sensitive to the inhibitory actions of lidocaine, tetrodotoxin, and of pindolol. The field-stimulus effect was enhanced by angiotensin and by bradykinin, but not by substance P. Only bradykinin exerted also a direct positive inotropic effect (in the absence of field stimulation). It is concluded that the intramural adrenergic neurons of the guinea-pig atrium have receptors for both angiotensin and bradykinin, but not for substance P.

Angiotensin II↗
PubMed1980

Anti-inflammatory effect of ethanol and other alcohols on rat paw edema and pleurisy.

The rat paw edema due to carrageenan, yeast, and dextran was dose-dependently antagonized by oral administration of ethanol. Carrageenan-induced paw edema was also inhibited by methanol, 1-propanol, and 1-butanol. The rat carrageenan pleurisy was reduced by oral pretreatment with methanol, ethanol, 1-propanol, 1-butanol, and dimethyl sulfoxide. Central depression, altered adrenal functions, increased osmolality, and hypothermia were no important factors for these actions of solvents. It is concluded that the inhibitory effect of ethanol on inflammatory responses increases the susceptibility of alcoholics to infection.

1-Propanol↗
PubMed1980

Antagonism of the gut-contracting effects of bombesin and neurotensin by opioid peptides, morphine, atropine or tetrodotoxin.

Morphine, met-enkephalin, beta-endorphin, tetrodotoxin (TTX), and atropine antagonized the gut-contracting effects of the peptides neurotensin and bombesin. The opioids and TTX shifted the concentration-response curves to the right and mostly depressed the maximum response to the agonists; atropine caused only depression of the maximum. Morphine was more potent than the opioid peptides. Naloxone did not modify the effects of neurotensin and bombesin. However, it completely abolished the antagonistic effects of the opioids, but not that of atropine. In conclusion, neurotensin and bombesin stimulate the intramural neurons via a process that is inhibited by the activation of opioid receptors.

Animals↗
PubMed1980

Failure of peptides (angiotensin, bradykinin, substance P, physalaemin, Met-enkephalin) to influence the cardiac action potential.

Angiotensin, bradykinin, substance P, physalaemin, and Met-enkephalin were tested for their ability to affect the action potential (AP) of the isolated guinea pig papillary muscle driven at 1/sec and 3/sec. Variables studied were height and duration of AP, dV/dtmax, half-life of recovery of dV/dtmax, and refractory period. At relevant concentrations the peptides were not effective.

Action Potentials↗