An injection of 2, 3-Dimercaptopropanol (BAL) (0.5 mg/10 g) into the abdominal lymphatic space induced a dispersion of the pigment in the melanocytes of the skin. In hypophysectomized frogs, however, BAL failed to induce the dispersion. A large amount of indolealkylamines, especially serotonin, was found in the skinof Rana nigromaculata (56.7 μg/g in the skin of frogs collected during autamun).Although seasonal variations were found in the serotonin level of the frog skin, BAL invariably decreased the serotonin level in each frog. In hypophysectomized frogs, however, BAL failed to decrease the serotonin level. From the above results, it is assumed that there is a certain correlation between serotonin level and melanocyte dispersion in the skin of frogs.
The influence of TDT administration in vivo on the changes of two enzymic activities in the liver cell membranes damaged by C Cl4 was observed. The following results were obtained. 1) In normal rats, TDT had no significant effect on NADH-cytochrome c reductase and ATPase activities in membranes or microsomes. 2) TDT was capable of preventing not only the changes of NADH-cytochrome c reductase and ATPase activities in cell membranes produced by C Cl4 administration, but also the leakage of NADH-cytochrome c reductase into plasma. 3) TDT did not modify the body temperature in normal rats and that induced by C Cl4, neither. 4) The mechanism of action of TDT was discussed.
Effect of various drugs containing the anti-inflammatory agents administerd subcutaneously and orally on the increasing activity of connective tissue permeability in rat skin of pronase P, α-chymotrypsin, hyaluronidase and histamine was tested by means of spreading method. (1) The relative order of the permeability increasing activity of 4 substances showed pronase P>α-chymotrypsin>hyaluronidase>histamine. (2) Na-salicylate, Aminopyrine, Bucolome, Indomethacin, Flufenamic acid and Prednisolone phosphate showed strong inhibition to the permeability indreasing effect of pronase P. However, Dexamethasone, Chloroquine diphosphate, Diphenhydramine Hcl, Homochlorcyclizine and Cyproheptadine Hcl had a slight or no effect. (3) The permeability increasing effect of α-chymotrypsin was inhibited strongly by Na-salicylate, Aminopyrine, Bucolome, Indomethacine, and Homochlorcyclizine and Cyproheptadine Hcl which had only slight inhibitory effect against pronase P. On the other hand, Phenylbutazone, Dexamethasone, Chloroquine diphosphate, Diphenhydramine Hcl and ε-aminocaproic acid had a slight or no effect. (4) Aminopyrine, Bucolome, Indomethacin and Flufenamic acid resulted in strong inhibition on the permeability increasing effect of hyaluronidase. (5) The increased permeability induced by histamine was antagonized by a number of drugs. Of these drugs, especially Homochlorcyclizine and Cyproheptadine Hcl inhibited strongly the effect of histamine. Na-salicylate, Aminopyrine, Phenylbutazone, Bucolome, Flufenamic acid and Chloroquine diphosphate and Diphenhydramine Hcl which had a slight or no effect to the other substances also inhibited strongly, whereas Indomethacin showed a weak activity only in this case.
By using dogs and cats, it was demonstrated that treatment with non-toxic doses of ouabain markedly enhanced the arrhythmic effects of catecholamines intravenously injected in the doses of 5 μg/kg. The production of ventricular arrhythmias by epinephrine or norepinephrine in digitalized animals was not prevented by a single injection of pronethalol or atropine, but it was prevented by combined administration of these too drugs. After stellate ganglia in both sides were removed, animals showed an increase in response to catecholamines which resulted in an induction of ventricular arrhythmias. The arrhythmias, in this case, was completely abolished by a previous administration of either pronethalol or atropine. Thus, it was sugges ted that ouabaininduced enhancement of arrhythmic effects of catecholamines is connected with sympathetic, vagal and myocardial factors.
Supplementary observations on the chemistry of Mercarbide, Mercuroform and their related substances. A) Mercuroform (M. F.) and Mercarbide (M.) 1) A certain kind of trimercuri-acetaldehyde (Trim. Acet. Ald.) such as Hofmann's nitrate and chlorate gives M. F-base and alkaliformate by the action of alkali, (M. F-decomposition.) Another group of Trim. Acet. Ald. such as Deniges' sulfate and OHC-C ?? yields M-base. [via the hypothetical substance, hydroxymercuroform. CH≡(HgOH)3] (M-decomposition) The only exceptional case is the reaction of OHC-C (HgCl)3 with Alkali by which Alkaliformate and M. F-dichloride, CH ?? are formed. 2) Trim. Acetone-(or Trim. Acetophenone-) nitrate gives acetyl-(or benzoyl-) -M. F. by the reaction with alkali without liberation of acetic (or benzoic-) acid and formation of M-Structure. 3) M. and M. F. are changed to their respective sulfates by the action of dil H2SO4 from which M is obtained by saponification. Thus, M. F. is able to be indirectly transfered to M. 4) When M is immers ed in aqueous solution of alkalihalide, it is perfectly changed to its halide (-Hg- ?? )n, however, the yield of M. F-halide ?? is always less than 50 % even by the immersion of long time. 5) M. reacts with conc. or dil. HX-acid to yield the substances CH≡(HgX)3 or CH ?? and these products are identical with those prepared from F. M. [X=Cl, Br] CH≡(HgI)3 and CH ?? are not obtainable by the action of HI, on either of M. or M. F, however, CH≡(HgI)3 can be easily prepared from M. by the action of (KI+I2)-reagent. The actio ns of dil HI solution on M. and M. F. are quite unique, i. e. M is easily transfered to its normal iodide -Hg- ?? )n, on the contrary, the yield of M. F-iodide ?? is always limited less than 30 % of theoretical value, even by the treating of long time with the renewed solution. Of the halogen derivatives of hydroxymercuroform, CH ?? is the only substance whith could not be obtained from either of M. or M. F. 6) Space formula of Mercarbide molecule was examined by Prof. UHARA and KATO basing on the following Physical data. Covalent radius; C, 0.77, 0, 0.66. Hg, 1.29 Å, Valence angle; C, 109°28′. O, 105°. Hg, 180°. It was concluded that the heteroring of M-molecule is twelve-membered irregular and non-coplanar hexagon composed of six atoms of Hg and each three atoms of C and O, and two radicals (-H, -HgOH) are combined with each C atom. B) a-Str. C=Hg and a′-Str. ( ?? -Hg-)n By the examination of behaviors of OHC-C ?? (Hofmann's formula.) its structure is assigned to gem-Dimercuripolymer type. ( ?? )n. (Matterson's expression). Heteroring of such substance is considered to be regular and coplanar pentagon composed of each five atoms of C and Hg. C) The latent polymeric structure of organo mercury compounds. Taking the cas e of OHC-C (HgCl)3 as an example, the present authors have presumed the polymeric structure of the products obtained by the reaction of Hg-salt solution with acetylene or acetaldehyde.
2-Methyl-4-amino-6-methoxy-s-triazine (CV 399) showed the marked central depressive actions in animal experiments, i. e. sedation in gross behavior, reduction of spontaneous motor activity and of hyperactivity induced by a variety of CNS excitants, potentation of pentobarbital or ethanol hypnosis, inhibition of hyperirritability of septal lesioned rats, analgesic effect, hypothermic effect and anticonvulsive action against electro- and chemoshocks. This agent blocked both of the conditioned avoidance response and the escape response in about the same extent in rats. This agent, however, did not exibit any effect on respiration and blood pressure level, and any change in brain serotonin content and in excretion of 5-hydroxyindole acetic acid in urine at the dose producing the above-mentioned effect.
The effect of 2-methyl-4-amino-6-methoxy-s-triazine (CV 399) on the central nervous system was evaluted in cats. All the arousal response induced by midbrain reticular formation and posterior hypothalamus stimulation, the recruiting and augmenting responses by nucleus centralis medialis and leminiscus medialis stimulation and the spindle burst by nucleus caudate stimulation were not affected by this agent in curarized cats. Spontaneous EEG was not significantly changed by single administration of this agent in curarized cats and by repeated administration subacutely in the cat with chronically implanted electrodes. On the other hand, the agent markedly prolonged the duration of after-discharges produced by dorsal hippocampus and lateral amygdala stimulation in acute preparations including “enceéphale isolé” cats and chronic preparations. These results suggest that the limbic system is most susceptible to this agent and the effect on this system is probably related to the clinical psychostimulant action of this agent.
Epinephrine and norepinephrine were injected into the femoral vein at a constant speed to compare the pressor effect before and after administration of digitoxin in dogs anesthetized with pentobarbital. It was shown that blood pressure rise caused by epinephrine and norepinephrine was enhanced after dogs were saturated with digitoxin. The enhancement of pressor response by digitoxin became more significant after atropinization. Pressor response to vasopressin, on the other hand, was not influenced by digitoxin administration. From these results obtained, a possible mechanism was discussed on the potentiation of catecholamine action by cardiac glycosides.
Oxazolazepam showed marked taming effects in mice, hamsters, rats and monkeys. These effects were comparable to those of chlordiazepoxide. Oxazolazepam was somewhat more potent against convulsions induced by megimide and pentetrazol and convulsion of E1-strain mouse but was less potent against convulsions induced by strychnine and electro shock than chlordiazepoxide. On the decrease of spontaneous locomotor activity, muscular relaxation, ataxia and loss of righting reflex in mice and tolerance of taming effects in hamsters, oxazolazepam was definitely less effective than chlordiazepoxide. On the conditioned avoidance response in rats, emesis produced by apomorphine in dogs and tremorine induced symptoms in mice, oxazolazepam was not significantly inhibitory.
On cardiovascular systems, oxazolazepam caused slight hypotension and depression of heart rate in larger doses but no significant effects on respiration, ECG and responses to autonomic drugs. These effects were weaker than those by chlordiazepoxide. On isolated organs, oxazolazepam exhibited more effect than chlordiazepoxide. Other effects, such as miosis, hypothermia, constipation and physical dependence liability were less demonstrated by oxazolazepam than by chlordiazepoxide. Emetic, antiinflammatory and diuretic actions were not seen by these drugs. Subacute toxicity by oxazolazepam for 5 weeks was definitely less than by chlordiazepoxide.