Electrocardiographic and behavioral effects ofl-DOPA in the guinea-pig

Conclusions The effects ofl-DOPA administered per os on conditioning, spontaneous behavior and the electrocardiogram of the guinea-pig are reported and compared.l-DOPA is able to inhibit the conditioned behavior in doses per os without any effect on spontaneous behavior or motility. Moreoverl-DOPA in doses up to 15 times higher than the average therapeutic daily dose pro kg used in man (TDD), does not alter the ECG of the guinea-pig. We did not observe ECG changes even after a total dose pro kg 60 times higher than TDD, which induced behavioral alterations in the 4 treated animals and one death.The present results may indicate psychotropic properties forl-DOPA and do confirm the low toxicity and cardiotoxicity of the drug, when supplied in a pure preparation of quality 12.

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Zusammenfassung Verabreicht manl-Dopa (1000 mg/kg per os) an Meerschweinchen, so kann dadurch das konditionierte Verhalten gehemmt werden, während das Spontanverhalten und die Motilität unverändert bleiben. Es sind keine Modifikationen des Elektrokardiogramms festzustellen, selbst dann nicht, wenn die 60fache mittlere therapeutische Tagesdosis gegeben wird.

     

3-Hydroxy-3-Methylglutaric acid and triton-induced hyperlipidemia in rats

Summary 3-Hydroxy-3-methylglutaric acid (HMG) significantly decreased cholesterol, triglyceride and phospholipid levels in whole serum, serum -lipoproteins and liver of Triton-induced hyperlipidemic rats. Therapeutically 50 mg HMG/kg is equivalent to 200 mg nicotinic acid/kg in lowering all these lipid parameters. HMG may exert its hypolipidemic effect through inhibition of lipoprotein synthesis.Acknowledgments. We are grateful to Dr.M. Saleemuddin for encouragement, Dr.P. E. Schurr, Upjohn Co. USA for generous gift of Triton W. R 1339 and Lady Tata Memorial Trust (India) for financial assistance to one of us (SYKY).     

Effects ofl-dopa alone and in combination with dopa decarboxylase inhibitors on the arterial pressure and heart rate of dogs

Zusammenfassung Nach Vorbehandlung mitl-HMD (peripherer Hemmer der Dopa-Dekarboxylase) wird mitl-Dopa (25 und 50 mg/kg i.v.) Blutdruck und Herzfrequenz herabgesetzt.     

Acute toxicity of dimethylnitrosamine in the presence of inhibitors of DMN demethylase

Summary The LD₅₀ of DMN was determined in groups of mice in the presence of inhibitors of DMN demethylase. Piperonyl butoxide, dibutylnitrosamine and nitrososarcosine had no effect on the acute toxicity of DMN. Diethylnitrosamine and DMN were markedly synergistic. All mice treated with 100 mg/kg diethylnitrosamine and 10.7 mg/kg DMN died. These results suggest that DMN demethylase may not be involved in theaacute toxicity of DMN.We thank Dr.D. B. Couch, Mr.E. J. Greene and Dr.A. E. Munson for their technical assistance.     

Selective blockade by mephentermine of reserpine-induced serotonin depletion

Zusammenfassung Die kombinierte i.v. Verabreichung von Reserpin (1 mg/kg) und Mephentermin (1 mg/kg) bewirkte Erregung in Kaninchen. Diese Erregung ist verbunden mit einem Verlust an Noradrenalin (NE) im Gehirn, nicht jedoch mit einem Verlust an Serotonin (5-HT). Aus den Ergebnissen lässt sich schliessen, dass die beobachtete Erregung von einem momentanen Ungleichgewicht zwischen NE und 5-HT im Gehirn herrührt.

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This study is supported in part by Career Development Award No. K3 NB 15279-09 and Grant No. MH 11189 from the National Institutes of Health, U.S.P.H.S. The authors wish to thank Dr.A. J. Plummer of CIBA Pharmaceutical Company for supplying the reserpine phosphate and Dr.R. J. Bower of Wyeth Laboratories for the mephentermine used in this study.     

Laktationshemmende Wirkung von N-[d-6-Methyl-8-isoergolin-I-yl]-N′, N′-diäthylharnstoff (VÚFB-6638)

Summary The inhibiting effect of orally administered N-[d-6-methyl-8-isoergolin-I-yl], N, N-diethylurea (VÚFB-6638) on the production of milk was found in rats. The inhibition of lactation was ascertained through the observation of the daily weightgains of the suckled puppies (ED₅₀=0.112 mg/kg/day) and through the observation of the presence of milk in the stomach of these puppies, as seen through their abdomen wall (0.084 mg/kg/day). This inhibition could be abolished with exogenous prolactin, which gives evidence that the drug studied acts via the endocrine system.

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Für die technische Assistenz danken wir FrauM. Kommersová und FrauV. Maitová.     

Reversible lenticular opacities induced in rats by emotional stress

Zusammenfassung Ratten (20 Tiere, 45 Tage alt) erhielten 150 mg/kg paraglynes Hydrochlorid s.c. injiziert. Akustischer Schock (2 h später) ergab bei 16 von 20 Tieren eine reversible subkapsuläre Linsentrübung.

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The authors wish to thank Mr. R. D.Lock for technical assistance.     

Zentralerregende Wirkung eines neuen Piperidinderivates

Summary A new piperidine derivative, the 2-diphenylmethylpiperidine, produces already in doses of 0.001 g/kg s.c. a strong increase of the spontaneous motility of various animals. On mice it has about the same potency as d-desoxy-ephedrine and is about 3 times more potent than amphetamin. It also acts markedly antagonistic on various narcotics but has practically no peripheral sympathomimetic effects.

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8. Mitteilung über Alkylenimin-Derivate. 7. Mitteilung sieheB. M. Iselin undK. Hoffmann, J. Am. Chem. Soc.76 (im Druck).     

Effect of the extracts fromAristolochia indica Linn. on interception in female mice

Summary The crude petroleum ether, chloroform and alcoholic extracts of the roots ofAristolochia indica (Linn.) showed 100% interceptive activity in mature female mice at the single dose of 100 mg/kg body wt. The follow-up studies with the chloroform extract showed the most significant effect in the basic part and two acidic fractions at the single dose levels of 50 mg/kg body wt. No toxic effect was observed at the dose levels used.The authors are thankful to Mr.P. P. Ghosh Dastidar, Medicinal Chemistry Division for the plant extracts. Thanks are also due to Indian Council of Medical Research and Council of Scientific and Industrial Research for granting scholarships to two of them (B.C. and A.D.) and to Prof.R. N. Chakravarti, Director of the Institute for encouragement.     

Induction of brain tumours in high yield by administration of N-ethyl-N-nitrosourea to newborn rats

Zusammenfassung Durch einmalige Verabreichung von 10 mg/kg N-Äthyl-N-Nitrosoharnstoff am 1. Tag nach der Geburt wurden bei 33/34 Ratten 53 Hirntumoren, 9 Tumoren des Rückenmarkes, aber nur 9 im peripheren Nervensystem erzeugt, was eine bedeutend gesteigerte Rate von Hirntumoren bedeutet.

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We thank MissMary Trumper and MissValerie Nash for technical assistance and the Cancer Research Campaign for financial support of C.E.S.     

Acceleration of turnover of14C-catecholamines in rat brain by chlorpromazine

Zusammenfassung Vorbehandlung mit 10 mg/kg Chlorpromazin (CPZ) i.p. bewirkt bei Ratten, denen¹⁴C-Tyrosin injiziert wurde, eine Zunahme der spezifischen Radioaktivität von¹⁴C-Dopamin im Gehirn. CPZ beschleunigt bei Tieren, deren zerebrale Katecholamine durchl-2¹⁴C-Dopa markiert wurden, den Abfall der spezifischen Radioaktivität von Dopamin und Noradrenalin. Daraus wird geschlossen, dass CPZ den Umsatz zerebraler Katecholamine erhöht.     

Serotoninantagonismus an der Placenta

Summary The placentae of 17 to 19 days pregnant mice respond to subcutaneous serotonin (15 mg/kg) with vascular changes which lead to the death of the fetuses in 3–4 h. Pretreatment of the females withd-lysergic acid derivatives preserves the life of the young. Thus, LSD showed an ED₅₀ of only 30 g/kg, while UML (Deseril®) gave an ED₅₀ of 3.7 g/kg. PML takes an intermediate position. At a 50% efficiency level, UML (Deseril®) antagonises the effect of a 4000 times higher dose of serotonin.     

l-DOPA administration to neonate chicks: Effects on behavior and levels of brain biogenic amines

Zusammenfassung Nachweis, dass bei Küken die i.v. Injektion vonl-Dopa (100 mg/kg) eine sofortige Überaktivität herbeiführt. Nach 10 min wurde im Gehirn eine Verminderung des Serotoningehaltes (14%) und eine Erhöhung des Dopamingehaltes (12fach) festgestellt, während Adrenalin, Noradrenalin und Histamin unverändert blieben.

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The author (JPH) was supported in part by a National Science Foundation Predoctoral Traineeship.     

Effects of three synthetic peptides analogous to neurohypophyseal hormones on the excitability of giant neurones ofAchatina fulica Férussac

Summary Deamino-dicarba-(d-d-)oxytocin andd-d-Arg-vasotocin at 10^–4 kg/l showed an excitatory effect on the periodically oxcillating neurone (PON) ofAchatina fulica Férussac.d-d-Arg-vasopressin had no effect.     

Stretching activity in dogs intracisternally injected with a synthetic melanocyte-stimulating hexapeptide

Riassunto La iniezione endocisternale nel cane di dosi fino a 0.75 mg/kg del sale acetico dell'esapeptide H. Glu (NH₂)-Ist-Fen-Arg-Tript-Gli.OH, svolgente un'attività melanoforo-stimolante della intensità di 2 × 10⁵ U/g, induce delle tipiche crisi di stiramento, del tutto simili a quelle che si ottengono iniettando per la stessa via dell'ACTH o dell'MSH. Dosi di 1.5 mg/kg invece non inducono più crisi di stiramento ma deprimono notevolmente gli animali e determinano una intensa scialorrea. Sembra di poter ammettere che la struttura chimica responsabile dell'effetto sui melanociti sia anche responsabile dell'induzione delle crisi di stiramento.

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We are indebted to Dr.R. Schwyzer, CIBA Ltd., Basle (Switzerland), for the synthetic melanocyte-stimulating hexapeptide.     

Sulfhydryl groups,copper, diphenylamine reaction and some enzymes in the serum of rats with 6-sulfanilamidoindazole arthritis

Zusammenfassung Bei oraler Gabe von täglich 125 bzw. 250 mg/kg 6-Sulfanilamidoindazol zeigten am 9. Tag 93% der Ratten Arthritis der hinteren Extremitäten. Im Serum waren Sulfhydrylgruppen um 40% abgesunken, Kupfer um 82% und Diphenylaminreaktion um 55% angestiegen. Die Fermente Lysozym, LDH, LAP und GOT sowie die Entzündungseinheiten blieben unbeeinflusst.

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Acknowledgments. 6-SAI was kindly supplied by Mr.Z. E. Mielens, Sterling Winthrop Research, Institute, Rensselaer, USA, and Prof. Dr.E. Hannig and Mr.C. Kollmorgen, Sektion Pharmazie, Halle. We thank Mrs.R. Wangemann for skilful technical assistance.     

Reduced foetal calcium without skeletal malformations in rats following high maternal doses of a strontium salt

Zusammenfassung nachweis, dass hohe Strontiumkonzentrationen die Kalzifikation der, Knochen neugeborener Mäuse, und diejenige in Knochengewebskulturen hemmen. Im Gegensatz dazu und zu anderen knochenaffinen metallen wirkt Strontiumnitrat in Dosen von25, 50, 100 and 200 mg/kg, verabreicht während des 9. bis 19. Trächtigkeitstages, bei Ratten nicht teratogen.

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We are indebted to Mr.K. L. Murray of the Government Chemist's Laboratory for analyzing tissue samples by atomic absorption spectrophotometry. We are also grateful toDr. R. F. Crampton, Director of BIBRA, for his interest and advice in this work.     

Inhibition of tyrosine degradation in vivo by the dopa decarboxylase blocking agent NSD-1034

Zusammenfassung Der Stoffwechsel von H ₃ ² -3, 5-l-Tyrosin wurde in mit NSD-1034 (100 mg/kg) vorbehandelten Versuchstieren (Hähnchen, katzen) untersucht. Als Folge des durch NSD-1034 stark gehemmten Abbaus entstanden während der Versuchszeit (ca. 20 min) nahezu kein Tritiumwasser und keine aromatischen Abbauprodukte. Auch die sonst zu beobachtenden radioaktiven Metabolite des H³-Tyrosins (Glutamin- und Asparaginsäure, Dopamin und Noradrenalin) waren nicht nachweisbar. Ausserdem war der Gehalt an H³-Tyrosin in Organen behandelter Tiere höher als in Kontrollen.     

Wiederherstellung des normalen Herzschlages nach elektrisch erzeugtem Kammerflimmern durch Adenosintriphosphorsäure

Summary (1) In the isolated mammalian heart (rabbit, cat, dog) electrically induced ventricular fibrillation is stopped in practically 100% of the cases by adenosin-triphosphoric acid (ATP) in doses of 0.25–20 mg, and the normal rhythm of the heart is permanently restored (as far as the experiment extends).(2) This effect of ATP follows from a primary blocking, which leads to a complete cessation of the activity of the ventricles with diastolic dilatation of the heart.(3) In as much as adenyl acid from yeast and adenosin (in large doses) also stop ventricular fibrillation, the energetic effect of ATP seems to be of no importance in stopping it; it is a specific effect of the adenyl compounds on the bundle ofHis.