1) After the administration of Nitrolime, narcosis induced by intravenous injection of alcohol 'was remarkably strengthened, but the rate of disappearance of alcohol from blood was not significantly altered. 2) The experiments proved that immediately after injection of alcohol, there was much more alcohol content in brain and liver in the Nitrolime-treated animal (albino rat) than in the control, but contrariwise the content in muscle was found to be less. These experiments indicate that at least the intensified alcohol narcosis observed after Nitrolime+ alcohol can be explained as a result of changes in the distribution of alcohol in the tissues, but it is possible that some of the symptoms are due to other substances formed.
1) After the administration of Nitrolime or Antabuse to rabbits, narcosis induced by itravenous injection of alcohol is remarkably intensified. Animals subjected to both kinds of treamtment show a much higher concentration of acetaldehyde in blood than do controls. 2) Immediately after i.v. injection of alcohol, Nitrolime-or Antabuse-treated animals (inbred albino rats (Wistar S.)) show a much higher concentration of alcohol in brain and liver but lower in muscle than do untreated animals, but formation of acetaldehyde in blood then is not greatly increased. The intensified alcohol narcosis, which is then induced, is probably due to the increased concentration of alcohol in brain. 3) Nitrolime-prepared human subjects are more sensitive to alcohol ; after intake of alcohol they show a much higher concentration of acetaldehyde in blood than do untreated subjects. Severe clinical reactions which are occasionally seen during Nitrolime-alcohol reaction were not seen during Nitrolime-alcohol reaction, and no pathological change was seen in EKG or in liver and kidney, but until sufficient data are accumulated, administration of Nitrolime should be considered as a dangerous procedure. Only further clinical trial can establish its uses and limitation.
In rabbits, the intravenous injection of HN2resulted in severe leucopenia and depression in serum cholinesterase activity, without change of electrophoretic pattern of serum. Administration of folic acid, cystein and methionine plus vitamin B12before injecting HN2, resulted in partial protection against the leucopenia induced by HN2. But administration of methionine and vitamin B12alone was less effective, even with large doses. The depression of the serum cholinesterase was related to the severity of leucopenia. One mechanism of HN2 action is inactivation of SH bearing enzymes but such mechanism is not the only possibility.
In a concentration of 2 per cent in the Ringer's solution, Vermizym (V) is capable of digesting living ascaris in about four hours. The optimum hydrogen-ion concentration for this effect is pH 5. The enzyme is irreversibly inactivated at pH 2 for one hour and also on being heated, to 80°C or above. For ascaris treatment, moderate effect was proved with the indicated dosage. There is no marked irritation of the gastrointestinal tract in a dog after ingesting relatively large dose of V and it does not increase previous damage to the gastric mucosa induced by the oral administration of hexylresorcinol, but parenteral injection of V causes severe tissue injuries. There are some evidences to show that V causes the liberation of a histamine-like substance and unidentified substance or substances, which slowly contract smooth muscles, from some mammalian tissues although this may not be of practical importance.
Observing the response to a radiant heat, or, to a pressure applied to the tails of mice, and also observing electro-physiological phenomena in cats as a target, an investigation was made regarding the influence of autonomic drugs upon the morphine analgesia. By the radiant heat method, adrenaline, ephedrine, methylpropamine and pilocarpine potentiated the morphine action, while ACh, mecholyl and prostigmine showed no such action. The above mentioned effects of adrenergic drugs were abolished by dibenamine, but not by priscol. A similar effect was also observed by the pressure method. When adrenaline or ephedrine was also combined, even a subthreshold dose (4 mg/kg) of morphine diminished the polysynaptic reflex disharge in the intact cats, although this effect was not observed in the spinal cats or in the thalamic cat.
The ergot cultivated on rye contains several kinds of alkaloids. The alkaloids of ergotoxine-and ergometrine-group have been found in fluid-extract of such cultivated ergot. Therefore, the hysterotonic action of extract is due to these ingredients. Furthermore, the blood pressure of rabbit can be lowered, too. On the excised intestine of rabbit, the extract diminishes the tension and the amptitude of autonomic movement. The vasoconstrictor action can be seen by Laewen-Trendelenburg's method. The movement of perfused toad heart has been depressed by the extract. These several actions of extract are weakened with the lapse of time. The grade of weakening is proportional to the acidity of extract. The weakening can be protected by ascorbic acid in some extracts.
The patterns of nicotine detoxication were studied in rabbits by the newly deviced colorimetric determination method with silicomolybdic acid the detoxicating ability was found in blood plasma and tissue extracts, such as of liver, lung, and of kidney, above all, in the liver extract the most potent.
Nicotine was determined either colorimetrically by the silicomolybdic acid method (see No. 7 of this Breviaria) and BrCN-anilin method or biologically by the isolated guinea pig intestine. The nicotine oxidation was studied by the manometric technique and also by Thunberg's method, and nicotyrine, an oxidation product, was determined by Ehrlich's pyrrole reaction, paperchro-matography and ultraviolet absorption spectra. The metabolic fate of nicotine in the rabbit liver extract was thus studied.
The structure-action relationship of above mentioned compounds was investigated. It was found in animal as well as in. human experiments, that of these compounds β-dimethylaminoethylbenzilic acid amide hydrochloride elevates pain threshold markedly and caused no untoward side actions. Its spasmolytic (anticholinergic) action on isolated rabbit's intestine was, however, remarkably weaker than that of the ester compound (β-dimethylaminoethylbenzilate hydrochloride).