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PubMedDate not supplied

Preliminary studies on effect of chloroquine phosphate on gastric acid secretion in rats.

It is not certain whether chloroquine-induced pruritus is mainly attributable to the liberation of histamine, a powerful gastric acid secretagogue from mast cells, which may not be beneficial in peptic ulceration. Therefore, the aim of this study was to find out whether chloroquine (CQ) can stimulate gastric acid secretion in the rat. Gastric acid output was measured by the continuous perfusion of rats stomachs under anaesthesia with normal saline at the rate of 1ml per minutes. Thirty albino rats were divided into five groups of six rats each. Three groups had intraperitoneal administration of the following; normal saline (1 ml/kg control), CQ (3 microgram/kg; test) and Histamine H2 receptor antagonist, Ranitidine [4 microgram/kg] following CQ administration respectively. The other two groups had subcutaneous administration of histamine (100 microgram/kg) alone and histamine following CQ administration respectively. The basal acid secretion, (4.71+/- +/- 0.05 mMol/10mins) in a group of rats was not significantly increased in comparison with the peak acid output [P < 0.05] following normal saline administration (1 ml; ml/kg; i.p.). Administration of CQ in a second group;significantly increased acid secretion to a peak of 7.2 +/- 1.7 mMol/10mins [P < 0.05]. Ranitidine blocked CQ -induced acid secretion in a third group. Histamine significantly increased acid secretion from control level of 4.85 +/- 0.14 mMol/10mins to 51.67 +/- 5.07 mMol/10mins [P < 0.001] in a fourth group, while CQ administered 2mins after histamine administration significantly increased acid level from 4.72 +/- 0.12 mMol/10mins to peak at 20.63 +/- 3.28 mMol/10mins [P< 0.001] in a fifth group of rats. The peak acid output in the fifth group was significantly lower than that obtained with histamine alone. In conclusion, chloroquine is a weak stimulant of gastric acid secretion rats. It inhibits histamine-stimulated acid secretion probably by occupying histamine H (2) receptors in rats.

Journal Article↗
PubMed1977

[The present state of hypotension (author's transl)].

The study was made of the recent literature on controlled hypotension and its place in modern anaesthetic practice. The effects of the different techniques and drugs are outlined in this paper. The results of investigation revealed that the circulation of heart, brain, liver, and kidneys is able to tolerate a wide range of deviation of blood pressure. Hypotension induced by high doses of halothane alone, which used to be considered as an adequate measure, has recently been shown to cause such serious side-effects that it can no longer be recommended. Halothane lowers blood pressure almost exclusively by means of a reduction of the contractility of the heart muscle. Ganglionic blocking agents alone should not be used either because of their depressing effect on the heart; moreover their hypotensive effects are hard to control. The sole exception is trimetaphan but it produces other severe side-effects such as liberation of histamine. On the other hand ganglionic blocking agents combined with halothane can be recommended. The combined administration of these drugs allow an easy control of hypotension and the side effects are minimal. Only sodium-nitroprusside meets all the requirements of a hypotensive drug. It operates selectively in a peripheral vasoplegic manner without effecting the cerebral centres. Regarding the heart, no side-effect is known apart from tachycardia; cardiac output is not altered. The metabolism of sodium-nitroprusside requires precaution in dosage, as degradation takes place via the toxic compounds of cyanide. Therefore liver disease and disturbances in vitamin B12 utilisation are regarded as contraindications for the use of nitroprusside. That is also the reason why a maximum allowable dose of 10-15 gamma/kg body weight and minute should not be exceeded. Prophylactic administration of vitamin B 12a (hydroxocobalamin) should be considered in every case when nitroprusside is used.

Cardiac Output↗
PubMed1989

[Anti-allergic properties of pipethiaden--a new preventive agent for migraine].

Pipethiadene, a prophylactic of vasomotoric headaches of the series of 4,9-dihydrothieno(2,3-c)-2-benzothiepine derivatives, shows a peripheralpharmacological profile of an antiallergic agent. The experiments in rats showed a high antianaphylactic effect of pipethiadene in the passive cutaneous anaphylaxis (PCA) test. Pipethiadene also exerted intensive antianaphylactoid action in rats on the liberator of histamine, compound 48/80, on dextran, and in the use of a combination of ovalbumin with indomethacin. In comparative pharmacological experiments with pizotifen and cyproheptadine an attempt was made to estimate the relative role of histamine and 5-hydroxytryptamine 5-HT) mediators in the employed experimental procedures in rats.

Anaphylaxis↗
PubMed1984

Effect of neuromuscular blocking drugs on arterial pressure and heart rate in rats.

The effects of neuromuscular blocking drugs on mean arterial pressure (MAP) and heart rate (HR) were studied in rats which were anaesthetised, tracheotomized and ventilated artificially. The arterial pressure was recorded from the carotid artery. Seven neuromuscular blocking drugs were injected intravenously at doses of 1, 5, and 25 mumol/kg. d-Tubocurarine, alcuronium and vecuronium lowered MAP in a dose dependent manner (maximum 40%). Succinylcholine, 1 mumol/kg, reduced MAP and HR, whereas the two larger doses increased them. Gallamine, 25 mumol/kg, or metocurine and pancuronium, 1 or 5 mumol/kg, each, induced short-lasting rises in MAP. Pancuronium, 25 mumol/kg, decreased MAP by 25%, while the largest dose of metocurine appeared to be toxic. The cardiovascular responses to neuromuscular blocking drugs were antagonized or abolished by pretreatment with the ganglionic blocking agent pentolinium. Pentolinium itself markedly reduced MAP and HR. After ganglionic blockade and restoration of MAP by noradrenaline infusion, all the neuromuscular blocking drugs induced short-lasting increases in MAP (10-30%), except d-tubocurarine which still reduced MAP by 30%, a fall which, in contrast to the effect in the absence of the pretreatments, was transient. This response to d-tubocurarine could not be abolished by a combined pretreatment with H1 and H2 antagonists showing that the hypotensive effect of this drug was not due to the liberation of histamine. These results suggest that the cardiovascular responses to neuromuscular blocking drugs in rats might be partly due to ganglionic effects. Other mechanisms are also involved since after the restoration of blood pressure by noradrenaline during the ganglionic blockade some cardiovascular responses to these drugs still occurred.

Animals↗
PubMed1982

Anti-allergic properties of ethyl-3-methoxyphenyl-4-thiazolyl-2-oxamate (F 1865).

F 1865 (ethyl-3-methoxyphenyl-4-thiazolyl-2-oxamate) has powerful oral anti-allergic properties in immediate hypersensitivity models in rats. In IgE-dependent passive cutaneous anaphylaxis (PCA) the ED50 was of 0.8 mg/kg. In IgG-dependent PCA the ED50 was of 0.6 mg/kg. This oxamate derivative inhibited the liberation of histamine during passive peritoneal anaphylaxis in rats at concentrations of 1 X 10(-6) M or higher. Doses of F 1865, active in PCA, had only weak anti-histamine and anti-serotonin effects, as measured by the increase of cutaneous capillary permeability. Likewise, its inhibitory effect on the bronchospasm due to histamine or serotonin in guinea-pigs was apparent only at doses of 1 mg/kg on i.v. administration. At doses of 100 mg/kg (X2) p.o., F 1865 was inactive against reverse passive Arthus pleurisy induced in rats by rabbit anti-bovine-albumin serum.

Amino Acids↗
PubMed1980

The role of cyclic amp in the process of specific hyposensitization.

The parenteral administration of a specific allergen produces a local edema due to the liberation of histamine. We have investigated the plasmatic cyclic AMPO in this reaction. A group of allergic patients (36 in all) with asthma or rhinitis or both diseases and with a very positive prick skin test was studied. The level of cyclic AMP was investigated before and after injecting the patients with the specific hyposensitizing extract. The average levels of cyclic AMP in our patients before the injection of the specific extract were 2.6 pmol/ml and this corresponded to the normal levels found in the controls in our laboratory (13.8 pmol/ml). After the injection of the allergen these levels increased by an amount that varied between 0.1 pmol/ml and 33.4 pmol/ml in 61.1% of the cases (p > 0.05). The cyclic AMP decreased by an amount that varied between 0.1 pmol/ml and 16.0 pmol/ml in 38.8% of the patients (p > 0.05).

Adolescent↗