Recently a-cocaine was prepared in this department under the direction of Dr. H. R. Ing by Dr. R. Foster. In the course of pharmacological experiments on the action of a-cocaine, which will be described in another paper, it was decided to test its action on the pressor effect of adrenaline when eserine had been given.The experiments were to be performed on cats, but as the supply of cats was short the observations were made in rats. It was then found that eserine had a pressor action in the rat, and the experiments now described were undertaken to analyse this action. During the course of the work a paper appeared by Dirnhuber and Cullumbine (1955) which also describes the pressor effect of certain anticholinesterase agents in the rat Since my observations confirm many of their findings, attention will be given mainly to new points or points of difference from them. METHODS In general, the method for recording the rat's blood pressure described by Crawford and Outschoorn (1951) has been followed. Rats (200-400 g.) of both sexes were used, and anaesthetized with 0.7 ml. per 100 g. of body weight of 25% urethane solution subcutaneously. To record the blood pressure a cannula was inserted into the carotid artery and connected with a mercury manometer, as described in detail by Condon (1951). A small polythene cannula, 0.5 mm. in diameter, was inserted into the jugular vein, and was used for injecting drugs. Before the experiment was started 1-1.5 mg./100 g. of heparin was injected. All doses of drugs were injected in 0.1 ml. and washed in with the same volume of saline. In most of the experiments artificial respiration was applied. The effect of eserine was the same no matter whether the animal was breathing naturally or not.The hindlegs of rats were perfused by inserting a cannula into the aorta immediately before the bifurca- RESULTSAction of Different Anticholinesterase Agents.-The effect of the intravenous injection of 10 ,g. eserine sulphate into a rat of 230 g. weight is shown in Fig. 1C. This amount of eserine, equivalent to 43 pg./kg., caused a rise of pressure equal to 50 mm. Hg which lasted for about 20 min. Such an effect was observed in 60 experiments varying from one rat to another only in duration; the longest duration was 45 min. and the shortest was 6 min. Dirnhuber and Cullumbine observed similar effects with samin (isopropylmethylphos- pentan-3-one) caused an insignificant rise. Neostigmine (Prostigmin methylsulphate) was also ineffective in causing a rise of pressure which was at all comparable with that produced by eserine. In three experiments the injection of 10 pg. neostigmine caused a fall of blood pressure. In one of these the injection of 30 pg. neostigmine caused a rise of 13 mm. and the injection of 100 p&g. caused a rise of 20 mm. In a fourth experiment the injection of 30 pg. caused a rise of 22 mm., but a repetition of the injection caused a fall.Action of Nicotine.-The pressor effect of eserine was found to be abolished in some rats by nicotine as shown in Fig. 2. At the. arrow 10 ,...

Ivermectin is one of the most commonly used drugs in pharmacotherapy of parasitic diseases in domestic and wild animals caused by parasitic nematodes and arthropods. However, ivermectin and other avermectins very often produce side-effects in hosts. The most dominant clinical symptom of ivermectin toxicity in domestic and wild animals is CNS depression. In nematodes, the target site of ivermectin's action is glutamate-gated chloride-channel receptor and GABA receptor. The depressive effect of ivermectin in mammals might include more than one mechanism; therefore, the anticonvulsive effect of ivermectin against convulsions caused by lidocaine and strychnine was evaluated. Ivermectin antagonized lidocaine- and strychnine-induced convulsions in rats, although these have different mechanisms. In the present study, the anticonvulsive ED50 ofivermectin for lidocaine-induced convulsions was 2.44 mg/kg (95% CL 1.67 to 3.57 mg/kg), whereas for convulsions induced by strychnine it was higher at 4.25 mg/kg (95% CL 2.32 to 3.78 mg/kg). At the same time, both anticonvulsive doses are significantly lower then the observed LD50 of ivermectin (18.20 mg/kg). Furthermore, flumazenil (0.1 and 0.2 mg/kg), an antagonist of benzodiazepine receptors, antagonizes just one part of these anticonvulsive effects of ivermectin. Our results show the significant anticonvulsive properties of ivermectin and support the findings that ivermectin in the CNS of mammals produces multiple inhibitory effects, probably through participation in the function of GABA-sensitive and GABA-insensitive chloride channels.

The introduction of substance P into the lumen of the isolated guinea-pig ileum caused an increase in the number and amplitude of the peristaltic waves. In preparations in which the peristaltic reflex was abolished, by fatigue, by external or internal application of 5-hydroxytryptamine, or by lowering the temperature of the bath, the introduction of substance P into the lumen of the intestine restored peristalsis. This effect of substance P was absent in preparations in which the mucous membrane was removed. Hexamethonium abolished the effect of substance P on peristalsis. It is concluded that substance P acts on the afferent nervous elements of the peristaltic reflex arc, possibly on the sensory receptors.Substance P has been found in relatively high amounts in the intestine and brain of various animals, such as the monkey, horse, ox, pig, sheep, dog, cat, rabbit and man (v. Euler and Gaddum, 1931;Douglas, Feldberg, Paton and Schachter, 1951;Ehrenpreis and Pernow, 1952;Pernow, 1953). A factor having, qualitatively and quantitatively, the same properties as substance P has been shown to occur in the intestine of the cod and the dogfish and in cod brain (v. Euler and Ostlund, 1956). The retina of the cow has also been found to contain high amounts of substance P (Duner, v. Euler and Pernow, 1954).The exact physiological role of substance P is still unknown. A central stimulating effect of substance P has been shown by v. Euler and Pernow (1954), and evidence has been presented that substance P stimulates afferent fibres (Lembeck, 1957). In evaluating the action of substance P on the jejunum of the rabbit, Blair and Clark (1956) concluded that the stimulant action of substance P on intestinal motility is mediated through a very labile mechanism which could well have a trophic influence on the amplitude of spontaneous contractions. It is known that the peristalsis elicited by increased intraluminal pressure is augmented in the presence of substance P (Gernandt, 1942). In the present experiments the effect of substance P on the peristaltic reflex was studied, introducing the substance into the lumen of the guinea-pig ileum. MATERIALS AND METHODSFor recording the peristaltic activity a modification of the method of Trendelenburg (1917) was used, which has been described in detail in a previous paper (Beleslin and Varagid, 1958). By this method it was possible to introduce the drug into the lumen of the intestine and to wash it out. The peristaltic activity was recorded by means of Stephenson's float recorder which records volume changes (Stephenson, 1948).The peristaltic reflex was tested by raising the intraluminal pressure (varying from 30 to 50 mm. in different experiments) for 90 sec. at constant intervals.Several experiments were done with preparations from which the mucosa had been removed. For this purpose a loop of intestine was turned inside out by slipping it over a glass rod. The mucosa was gently scraped off using a piece of filter paper, and then the loop of intestine was returned to its normal position...

No abstract

No abstract