ANALGESIC PROPERTIES OF SUB-ANAESTHETIC DOSES OF FLUORINATED ANAESTHETICS IN THE MOUSE.
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Biomedical subjects
Publications and source records attributed to J M ROBSON.
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The anti-inflammatory effect of various substances was measured in rats implanted with cotton wool pellets. Injection or implantation of irritant materials decreased the deposition of granulation tissue on the pellets. As the amount of irritant material increased there was a corresponding decrease in the amount of tissue deposited on the pellets. There is evidence that this could not be explained by a limit to the amount of granulation tissue available within the body, and competition for it between the cotton pellets and the implanted substances. An alternative hypothesis that an anti-inflammatory substance is produced at the site of irritation (the site of implantation of the irritant substance, such as polyester sponges) was investigated. The evidence obtained supports this hypothesis. Inflammatory exudate, squeezed from polyester sponges which had been implanted subcutaneously in the backs of adrenalectomized rats. The substance responsible for this effect is probably not a steroid, and is not normally present in the plasma of adrenalectomized animals. There is, however, some (although not conclusive) evidence that it is present in the plasma of animals in which sponges have been implanted. It does not appear to be produced by incubation in vitro of plasma with sponge. The significance of these observations is discussed.
An electrical method of testing for analgesia in mice has been developed for use with inhalation anaesthetics given in sub-anaesthetic concentrations. The anaesthetic drugs are administered in a gas chamber designed for the testing of analgesia without removal of the animals from the chamber.
Trichlorethylene in a sub-anaesthetic concentration (0.5% v/v in oxygen) has an analgesic effect on mice, which develops slowly and reaches a maximum roughly equivalent to that produced by 5 mg/kg of methadone hydrochloride given by intraperitoneal injection. Ethyl chloride causes analgesia in sub-anaesthetic concentrations (3%) but is much less potent than trichlorethylene. Halothane (0.75%) produces slight but definite analgesia. Cyclopropane and diethyl ether have no appreciable analgesic effect. Concentrations of nitrous oxide (up to 90%) in oxygen lack any observable analgesic action on the mouse. Trichlorethylene is considerably potentiated by nitrous oxide, its anaesthetic rather than its analgesic action being affected. Nitrous oxide (40%) potentiates the analgesic rather than the anaesthetic action of halothane (0.75%). However, increasing the concentration of nitrous oxide to 60% causes the anaesthetic action of halothane to predominate.
5-Hydroxytryptamine (5HT) levels were measured in blood and tissues from pregnant mice. Blood levels remained constant during pregnancy and were the same as those in nonpregnant female mice. Placental levels of 5HT increased throughout pregnancy as did the foetal levels. The maternal blood volume of the placenta also increased with advancing gestation. 5HT levels were measured after treatment of the mother with 5HT, and the critical placental level of 5HT observed at about the time of death of the foetus was determined. The levels of 5HT in the placenta and foetus after treatment of the mother with several monoamine oxidase inhibitors were measured, and found to show no significant increase above the normal levels in these tissues. Treatment with cyproheptadine, a 5HT antagonist, did not delay parturition.
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The subcutaneous injection of a single dose of 5-hydroxytryptamine into pregnant mice produced a large number of fetal abnormalities, mostly of the eyes, limbs, and tail; the skull and central nervous system were also sometimes affected. These effects could result from the action of the drug on placental function and blood supply.
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As 5-hydroxytryptamine can interrupt pregnancy in all its stages in mice and as pregnancy can be protected from the action of 5-hydroxytryptamine by either progesterone or by prolactin only in early (days 1 to 6) but not in late pregnancy (day 14), the present experiments with two antagonists of 5-hydroxytryptamine, namely methysergide and cyproheptadine, were carried out. Each compound antagonized the action of 5-hydroxytryptamine in late pregnancy. The toxic effects produced by 5-hydroxytryptamine are probably due to a direct action on the placental circulation which is prevented by the antagonists. In early pregnancy, methysergide prevented the effect of 5-hydroxytryptamine, which is believed then to act on the central nervous system, interfering with luteal activity. Cyproheptadine alone interrupted early pregnancy, an action which was prevented by progesterone.
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