Activité antifibrillante chez l'animal d'un nouveau dérivé de la phényl-éthylamine

Summary A new synthetic phenyl-ethyl-amine derivative, the 2-[N- (3, 4-methylen-dioxyphenylethyl)-methylaminomethyl]-tetrahydrofuran, No. 11 081, exhibits a strong protective effect against cardiac fibrillation and arrhythmias produced by various experimental methods: against fibrillation due to aconitine 3 × 10^–8 on the isolated cat's heart, it is active in a concentration of 10^–6–2 × 10^–6. Against cardiac arrhythmias produced in the cat by adrenaline + CHCl₃ or cyclopropane, it shows a protective effect by 5–10 mg/kg i.v. and even perorally by 50 mg/kg. In these tests, the antifibrillatory activity of the new compound seems to be roughly the same as that of -fagarine, and higher than that of procaine.

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9^e communication sur les dérivés des alcoylène-imines; 8^e communication, cf. Exper.10, 261 (1954).     

Dopamine and cerebral cortical blood flow in the rat

Summary Dopamine topically applied to the cerebral cortex (1–20 g/ml) or administered i.v. (0.5–64 g/kg/min) has no effects on cerebral cortical blood flow in the rat.     

Conduction velocity of peristaltic waves in the in vivo ureter: application of a new diameter gauge

Summary The conduction velocity of peristaltic movements of the canine ureter was measured under anaesthesia with a new type of diameter gauge using an image sensor. The peristaltic velocity was 34.1±6.2 mm/sec in 10 experiments. Noradrenaline at a low dosage of 1 g/kg i.v. reduced the resting diameter, increased the conduction velocity to 47–56 mm/sec, and approximately doubled the frequency of contraction. The application of acetylcholine also caused an increase in both frequency and conduction velocity (42–46 mm/sec). A plot of the conduction velocity against the mean period of peristaltic contraction was hyperbolic in shape.     

Anticonvulsant action of YG 19-256 in baboons with photosensitive epilepsy

Summary YG 19-256, 4-(1,3,4,9b-tetrahydro-5 methyl-2H-indeno[1,2-c]pyridine-2-yl)-2-butanone methane sulphonate, 1–3 mg/kg i.v., abolished or reduced photically-induced myoclonic responses for 1.5–6.5 h in baboons,Papio papio, without producing signs of acute neurological toxicity.We thank the Medical Research Council, The Wellcome Trust and the British Epilepsy Association for financial support, and Drs D.M. Loew and H. Weber (Sandoz Ltd) for the gift of YG 19-256.     

Über den Phytoöstrogengehalt einiger Pflanzen

Summary The quantity of phyto-estrogens in red clover, hop, peas, and cabbage was estimated by titration on castrated female rats and infantile mice. The level of phytoestrogens was as follows: in hop 1050–2000/kg, in peas 4–6/kg, in cabbage 24/kg, and in red clover 6–9/kg. The author supposes that the sexual disorders described byRosenberger ¹⁴ in cows fed with cabbage, can be explained by the presence of phyto-estrogens in this plant.     

Participation of ACTH1–10 and ACTH4–10 on the melatonin modulation of benzodiazepine receptors in rat cerebral cortex

In this study, we examined the effect of intracerebroventricular (i.c.v) injection of melatonin and/or ACTH_1–10 and ACTH_4–10 on [³H]flunitrazepam binding sites in the cerebral cortex of hypophysectomized rats. Hypophysectomy increased the B_max (maximum number of binding sites) of benzodiazepine (BNZ) receptors for at least 7 days after surgery, without changing K_D (dissociation constant). The i.c.v. injection of melatonin to hypophysectomized rats significantly increased B_max, whereas the same doses of melatonin were ineffective in sham-operated animals. In both cases, K_D values were unchanged. The i.c.v injection of ACTH_1–10 to hypophysectomized animals significantly increased B_max, an effect that was enhanced by simultaneous i.c.v. injection of ACTH_1–10+melatonin, reaching higher values of B_max than the i.c.v. injection of these hormones individually. No significant changes in K_D values were found after ACTH_1–10 and/or melatonin administration. However, the i.c.v. injection of ACTH_4–10 to hypophysectomized rats did not change B_max, although it significantly increased K_D values, indicating a decrease in the BNZ binding affinity. Melatonin injection counteracted this effect of ACTH_4–10, returning K_D to the control value. Moreover, although the lower dose of i.c.v. melatonin used, 10 ng, was unable to modify B_max of BNZ binding in the ACTH_4–10-injected group, the higher dose, 20 ng, significantly increased B_max. The results suggest that these ACTH-derived peptides can modulate the effect of melatonin on brain benzodiazepine receptors.     

A centrally induced vasodepressor response after intravenous administration of whole venom ofNaja mossambica pallida in cats

Summary Naja mossambica pallida venom administered i.v. (300 /kg) produces an initial brief fall in blood pressure, due to a direct myocardial depressant effect, and a sustained fall due to central depressant effect.This study was supported by University of Nairobi research grants (670–376). We also thank Mr E. Njogu for photographic assistance.     

Rat mammary cancer inhibition by a prolactin suppressor, 2-bromo-α-ergokryptine (CB 154)

Zusammenfassung 2-Br--Ergokryptin (=CB 154) wurde täglich während 80–100 Tagen, beginnend mit der Carcinogenapplikation, DMBA - (5 mg i.v.)-behandelten weiblichen Ratten in der Dosis 6 mg/kg i.p. verabreicht. CB 154 bewirkte ein verzögertes Erscheinen und ein langsameres Wachsen der Mamma-Tumoren sowie eine verminderte Todesrate der carcinogenbehandelten Ratten.     

Intrarenal circulation in mercuric chloride-induced renal failure

Zusammenfassung Durch simultane Ermittlung der totalen und der nutritiven Nierendurchblutung wurde festgestellt, dass 1. in der normalen Hundeniere die gesamte Durchblutung durch die Kapillaren strömt; 2. 3 Tage nach i.v. Verabreichung von 2 mg/kg Sublimat etwa 1/3–2/3 der totalen Durchblutung durch arteriovenöse Anastomosen geleitet werden und 3. die kapillare Durchblutung umso mehr abnimmt, je schwerer die Symptome der Sublimatvergiftung sind.     

Influence of flupirtine,a novel nonopioid analgesic agent on somatosensory evoked potentials in rats

The effect of flupirtine, a novel nonopioid analgesic, on somatosensory evoked potentials (SEP) was investigated in anesthetized rats. Primary somatosensory potentials were evoked in the cerebral cortex by stimulation of the skin of the whiskery part of the face. Flupirtine injected i.p. dose-dependently prolonged the latency and reduced the amplitude of SEP with ID₅₀-values of 5.4 mg/kg (2.6–9.3 mg/kg) and 7.9 mg/kg (3.9–13.8 mg/kg), respectively. This effect of flupirtine (10 mg/kg, i.p.) on the latency and the amplitude of SEP, did not change when naloxone (1 mg/kg, i.p.) was given before flupirtine. The results indicate that the analgesic flupirtine decreases the primary somatosensory evoked potential by diminishing the excitability of cortical neurons. Opioid mechanisms are not involved.     

Interaction of CDP-choline with synaptosomal transport of biogenic amines and their precursors in vitro and in vivo in the rat corpus striatum

Summary Added to a striatal synaptosomal homogenate of rat brain, CDP-choline 10^–4 M inhibits the uptake of norepinephrine (NE), dopamine (DA) and serotonin (5 HT) in a competitive fashion and enhances the uptake of tyrosine and tryptophan; administered to animals, CDP-choline (50 mg/kg/l h/i.v.) inhibits only the in vitro uptake of DA but enhances the uptake of precursors.This research was supported by CNRS grant (ERA No. 560) and Inserm grant (FRA 5).     

Nitric oxide-related pancreatic endocrine responses to hyperglycaemia in the conscious calf

Mean plasma insulin concentration was reduced and mean plasma glucose concentration increased following the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mol kg^–1 i.a.) in conscious calves given continuous infusions of exogenous glucose (30–60 mol min^–1 kg^–1 i.v.). It is concluded that the rise in plasma insulin concentration which occurs in these animals in response to glucose is mediated, at least in part, by a nitric oxide-related factor (NOx).     

Cerebral vascular action of bradykinin in the dog

Zusammenfassung Die Wirkung von natürlichem und synthetischem Bradykinin auf den cerebralen Kreislauf wurde beim Hund in Chloralosenarkose durch die Registrierung des intracraniellen Venendruckes und Blutausflusses und des Nasenhöhlenplethysmogrammes untersucht. Bradykinin erzeugt in Dosen von 0.5–3 µg/kg i.v. eine deutliche Erweiterung der Hirngefässe, analog der durch eine gleiche oder etwas niedrigere Menge von Histamin hervorgerufenen. Im Gegensatz zum Histamin übt Bradykinin in dieser Dosierung keine erweiternde Wirkung auf die Nasenhöhlengefässe aus. Die durch Bradykinin erzeugte Zunahme der Gehirndurchblutung wird durch Neoantergan oder Atropin nicht gehemmt.     

The effect of an ethanol extract of catnip (Nepeta cataria) on the behavior of the young chick

Summary The alcohol extract of catnip has a biphasic effect on the behavior of young chicks. Low and moderate dose levels (25–1800 mg/kg) cause increasing numbers of chicks to sleep, while high dose levels (i.e. above 2 g/kg) cause a decreasing number of chicks to sleep.     

Involvement of H1 receptors in the central antinociceptive effect of histamine: Pharmacological dissection by electrophysiological analysis

Intracerebroventricular (i.c.v.) administration of histamine (HA, 0.025–0.1 M/rat) to arthritic rats induces a dose-related inhibition of the neuronal thalamic firing evoked by peripheral noxious stimuli. To characterize the type(s) of HA receptors involved in this depressing activity of the amine we used electrophysiological techniques to examine the effects of i.c.v. administration of H₁ and H₂ agonists and antagonists on the spontaneous and evoked nociceptive firing of the thalamic neurons in rats rendered arthritic by Freund's adjuvant. The H₁ agonist 2-pyridylethylamine (0.4–1.0 M/rat, i.c.v) displayed a dose-dependent antinociceptive effect very similar to that of HA, while the H₂ agonist dimaprit (0.05–0.2 M/rat, i.c.v.) did not modify thalamic firing. Neither mepyramine (H₁ antagonist, 0.1 M/rat, i.c.v.) nor zolantidine (H₂ antagonist, 0.01 M/rat, i.c.v.) modified the evoked firing of rat thalamic neurons. When administered before HA (0.1 M/rat, i.c.v.) mepyramine but not zolantidine was able to inhibit the antinociceptive effect of HA. On the basis of the present electrophysiological results, we suggest that a specific interaction of histamine with H₁ receptors may be important for its antinociceptive effect on afferent peripheral inputs to the thalamus.     

Activation by S-adenosylhomocysteine of norepinephrine and serotonin in vitro uptake in synaptosomal preparations from rat brain

Summary S-Adenosylhomocysteine (10^–7–10^–5 M) activated norepinephrine (NE) and serotonin (5HT) in vitro uptake in synaptosomal preparations from rat brain, but did not affect dopamine (DA) uptake. When administered to rats (7 mg/kg i.p.), it had the same effect on in vitro NE and 5HT uptake. It did not affect NE and 5HT release.Work achieved within the frame of the research contract institut Mérieux., Institut National des Sciences Appliquées.     

In vivo inactivation of transglutaminase during the acute acrylamide toxic syndrome in the rat

Summary The activity of liver and brain transglutaminase is rapidly lost following i.p. injection of acrylamide (50–200 mg/kg). Other enzymes investigated were not modified by the treatment, with the exception of brain enolase.     

Failure of (+)-naloxone to accelerate feline colonic transit

Summary To determine whether the colonic transit accelerating effect of (–)-naloxone (0.3 mg/kg, i.m.) is due to an action at opioid receptors or a direct pharmacologic effect, its enantiomer, (+)-naloxone (0.3 mg/kg, i.m.) was administered to cats and compared to saline control using colonic transit scintigraphy. Transit was not accelerated by (+)-naloxone. The effects of naloxone on colonic transit are thus stereospecific, and are probably mediated by opioid receptors.     

The levels of metallothionein-like proteins in animal tissues

Summary The level of metallothionein-like proteins was determined in different tissues of 6 animal species. The highest concentrations were found in pig and rat tissues. The organs richest in metallothionein-like proteins included: kidneys (101–305 g/g), intestine (127–257 g/g) and liver (54–496 g/g).Studies performed under the Polish-American agreement 05-009-2 with National Institute for Occupational Safety and Health, PHS, USA.     

Effect of vasopressin on hepatocytic and ductal bile formation in the dog

Zusammenfassung In Studien an 8 cholecystektomierten, mit einerThomas-Kanüle versehenen, nicht-anaesthesierten Hunden konnte nach i.v. Injektion von 0,5 E pro kg Körpergewicht Lysin-8-Vasopressin eine Erhöhung des Gallenflusses um durchschnittlich 55% beobachtet werden. Da die biliäre Clearance von¹⁴C-Erythritol — ein Mass des canaliculären Gallenflusses — gleichzeitig anstieg, die Cholerese aber als Zusatz einer HCO₃ —und Cl^– reichen Flüssigkeit imponierte, scheint es wahrscheinlich, dass Vasopressin hepatocytäre und ductuläre Mechanismen der Gallenbildung beeinflusst.