Animals receiving catecholamines on awakening from barbiturates anesthesia returned to sleep. Furthermore, animals pretreated with adrenaline showed a significant prolongation of thiopental sleeping time. The analytical data demonstrated that this potentiating effect of catecholamines which was blocked by the adrenolytic agents was attributed to an increased penetration of thiopental into the brain. On the basis of in vitro experiment, the possibility that adrenaline might exert the potentiating effect on the thiopental anesthesia through its lipolytic action was suggested.
The potentiating effect of oleate on the thiopental anesthesia was confirmed by the following: 1) prolongation of sleeping time, 2) return to sleep on recovery and 3) reduction of anesthetic doses. An intravenous administration of oleate to animals under thiopental anesthesia was found to increase the brain thiopental levels. From the results of in vitro thiopental penetration experiment, it was found that oleate increased unbound, freely diffusible thiopental. This increase was probably due to the capacity of the fatty acid to usurp albumin binding sites of thiopental. The inhibitory effect of various fatty acids on thiopental binding to albumin was studied by the technique of ultrafiltration.
Effects of Natulan, which had been proposed to be antitumor and monoamine oxidase inhibiting agents, on the cardiovascular system and intestinal movements were studied using rabbits, dogs, cats and guinea-pigs. When Natulan was administered intravenously, it caused slight excitation of respiration, depressor effect on blood pressure and no effect on cardiac movements in rabbits, and hypotension in cats, while it brought about weak hypertension and positive chronotropic effect in dogs. Natulan inhibited movements of isolated guinea-pig heart and rabbit atria. Pressor and positive chronotropic effects in dogs were eliminated by antiadrenergic agents, and these effects were diminished by repeated administration. Prior administration of reserpine exhibited that sympathomimetic effects of Natulan were potentiated in dogs, while depressor response was reversed to pressor response in cats. Natulan inhibited the blood pressure responses to carotid occlusion and vagus stimulation, and tended to inhibited the responses to splanchnic stimulation and dimethylphenylpiperadinium. Natulan inhibited movements of isolated intestine and induced slight inhibition followed by weak excitation in situ. These pharmacological responses to Natulan were observed when it was administered in large doses.
Natulan brought about a sedative effect with neither hypnotic nor anesthetic effect in the rabbit, and showed a drowsy pattern in the spontaneous EEG activity. The EEG arousal response to auditory was markedly depressed by Natulan, while the arousal response elicited by electrical stimulation of the midbrain reticular formation tended to be depressed by this drug. The recruiting response was not influenced by the drug. Locomotor activity of the rat in open field test was not affected by Natulan, and the drug did not induce an analgesic effect and a muscle relaxing effect in inclined screen test in the mouse. The drug prolonged hexobarbital induced sleeping time in the mouse and showed a weak cataleptogenic effect in the mouse. Natulan elicited a anticonvulsive effect on pentetrazol convulsion, whereas it showed no influence upon maximal electroshock convulsion. These pharmacological effects of Natulan were observed when it was administered in large doses. From the result, it has been suggested that Natulan acts inhibitory on the central nervous system when it is used in large doses.
a) When Mercarbide and Mercuroform are warmed at 50-60° for 80 hrs in etherial solution of ethyl iodide, the former changes to Iodomercuroform HC≡(HgI)3 and the latter to Mercuroform diiodide. HC ?? b) By immersion of Mercarbide-chloride, Mercuroform-dichloride and Chloromercuro-form in ammoniacal water saturated with ammonium chloride, ammine compounds of respective chloride (-Hg- ?? )3, HC ?? and HC≡[Hg(NH3)Cl]3 are formed as sparingly soluble gray white amorphous bodies. c) Mercarbide-Sulfate (-HG- ?? )3=C3H3O3Hg9(HSO4)3, when immersed in KCl (and KBr) solution for 5 hrs at 80° liberates two of HSO4-group as SO411 to be dissolved in the solution and externally applied halogen ions take the place to form HgX-group. At the same time, an oxygen atom of oxide-linkage separates out from heteroring system leaving behind a chain structural molecule and two more halogen atoms combine to Hg-atom bonded on ends of the chain newly formed. Throughout these reaction sequence one of Hg(HSO4)-group remains unchanged. (HSO4)-Hg- ?? →(HSO4)-Hg- ?? →(HSO4)-Hg- ?? C3H3O3Hg9(HSO4)3+4KX→C3H3O2X4Hg9(HSO4)+2K2SO4+H2O Deniges' Substance, Formyl derivative of Mercarbide-Sulfate. (-HG- ?? )3=C6H3O6Hg9(HSO4)3 behaves similarly as above in anion exchange reaction with KCl (KBr) to form C6H3O5Cl4Hg9(HSO4) and C6H3O5Br4Hg9(HSO4) respectively as the end products (HSO4-Hg- ?? [R=CHO] Mercarbide (-Hg- ?? )3=C3H3O3Hg9(OH)3. In the old days, anion exchange reactions of Mercarbide in KBr (KCl) solution were reported by K. A. Hofmann. Since the group (HO)-Hg- in Mercarbide molecule ought to be corresponding to (HSO4)-Hg-group in molecule of Mercarbide-Sulfate, the end products from Mercarbide should be C3H3O2X4Hg9(OH). (HO)-Hg- ?? The analytical data of these end products reffered in Hofmann's past report agreed prefectly with above conception. d) Mercuroform: Basing on various facts related to anion exchange reactions of Mercuroform and its salt, it is surmised that the structure of these substances might be dimer of Methanoxy trimercarbide. ?? Such a heterocyclic system should be much more stable than that of Methanoxytrimercarbide and a little labile than that of Mercarbide. Though it is quite rational to think the structure of Methanoxytrimercarbide HC ?? to be prototypical form for the substances of this series, it seems rather doubtful whether such a substance could be actual molecule of Mercuroform or not.
Isolated cat and guinea-pig hearts were perfused with 10-7M 3H-ouabain or 3H-digitoxin for 30 min. The subcellular distribution of cardiac glycosides was investigated. (1) In cat hearts, the digitoxin uptake was approximately 6 times greater than the ouabain uptake. Upon fractionation, the concentration of glycosides in the microsomal fraction was the highest, being 8 ?? 17-fold range of that seen in the other fractions. (2) In guinea-pig hearts, the subcellular distribution of glycosides showed the same pattern as in cat hearts. (3) From these findings, it was suggested that cardiac glycosides might have a greater affinity to microsomal fraction regardless of animal species.
The binding capacity of ouabain or digitoxin by sarcoplasmic reticulum (SRF) isolated from cat heart muscle was found to be about 7-9 times as much as that by cell membrane from cat heart muscle. Acetone treatment of SRF caused a marked decrease in the binding capacity of ouabain and digitoxin. SRF pretreated with phospholipase C was decreased in content of phospholipid, in the ATPase activity, in the Ca-binding capacity and in the binding capacity of ouabain or digitoxin, while SRF pretreated with digitonin was decreased in content of cholesterol, but not in phospholipid content, in ATPase activity, in the Ca-binding capacity and in the binding capacity of ouabain or digitoxin. From these findings, it might be concluded that SRF was the major binding site for cardiac glycosides and that the content of phospholipid of SRF plays an important role in the drug-binding capacity.
Present study was undertaken to determine whether distress with reserpine is protected with chronic administration of central acting drugs (MAOI, 5HTP and DOPA) and adaptation hormones (ACTH and cortison) Methods and materials: Male rats of wistar strain, weighing 70-90 g, were maintained on high sucrose diet and 5 % sugar solution near for 30 days. Rats were intramuscularly injected with physiological saline solution (2.5 ml/kg) as control animals, with reserpine (1.25 mg/kg) to induce distressed state, with isocarboxazide (MAOI, 2.0 mg/kg), 5HTP(2.0 mg/kg) and DOPA (100 mg/kg) to produce serotonergic or/and adrenergic state, with ACTH (5 mg/kg) or cortison (20 mg/kg) to activate homeostatic state and in combination with reserpine and MAOI, 5HTP, DOPA, ACTH or cortison to observe the antagonism or interaction between reserpine and other drugs, every other day, for this period. Blood sugar determined spectrophotometrically by method of Asator-King and liver glycogen extracted as described by Fujii and finally determined by Asator-King methodwere measured as the indicator on the degree of defensive reactions. The results are summed up as follows: 1) Hypoglycogenesis of rat liver by reserpine was inhibited in combined administration with MAOI or cortison, but accelerated further with 5HTP, DOPA or ACTH, while the independent administration of MAOI, 5HTP, DOPA or each hormones (ACTH and cortison) produced the hyperglycogenesis. 2) Reserpine-hyperglycemia was further enhanced in combination with MAOI, DOPA or ACTH, but not with 5HTP or cortison, while hyperglycemia was produced in rats treated independently with MAOI or cortison but not with 5HTP, DOPA or ACTH.
The anti-secretory and antiulcerogenic activities of a substance, which was a glycopeptide (abbreviated as GGP) and extracted from the mucosa of the third stomach of the finback whale (Balaenoptera physalus L.), were studied in detail. GGP was shown to have a dose-dependent anti-secretory effect on gastric secretion in the Shay's rats with ligated pylorus with intravenous doses of 0.01-2.0 mg/kg. GGP showed a significant suppressing effect on gastric secretion induced by histamine, acetylcholine and tetragastrin in the Schild rats, and also showed the similar effect on histamine- or tetragastrin-induced secretion in the Heidenhain pouch dogs. Not only GGP showed the significant antiulcerogenic activities against the Shay rat ulcers and such experimental peptic ulcers as serotonin, histamine and stress ones, but also is exhibited a definite curative effect on the ulcer induced by acetic acid injection. GGP may induce the anti-secretory effect through direct or indirect inhibition of activity of parietal cells, and the antiulcerogenic effect of GGP may be produced through antisecretory effect.