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.     

Blockade of GABAB receptors accelerates amygdala kindling development

The aim of this study was to investigate the putative role of GABA_B receptors in the development of amygdala kindling in rats. The effects of the GABA_B blocker CGP 35348 and the GABA_B agonist baclofen on the progressive development of behavioural seizure symptoms (stages 1–5 classified by Racine) and duration of afterdischarges (AD) were studied. CGP 35348 at a dose of 300 mg/kg i.p, which blocks central GABA_B receptors, moderately but consistently accelerated the development of behavioural seizure symptoms. CGP 35348 had no marked effect on the duration of ADs corresponding to the different seizure stages. L-baclofen (6 mg/kg i.p.) had a dual effect on kindling development. It retarded the development of the behavioural symptoms, but increased the duration of AD. In conclusion, the results suggest that synaptically-released GABA activated GABA_B receptors and thereby exerted a depressant effect on kindling development.     

Stimulierung der Atmung durch Bradykinin und Kallidin

Summary In guinea pigs and rabbits small doses of bradykinin and kallidin (1–8 µg/kg i.v.), which have no bronchoconstrictor effect, stimulate respiration causing tachy- and hyperpnea. Bilateral vagotomy as well as salicylates (4–40 mg/kg i.v.) abolish these respiratory responses.     

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.     

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.     

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.     

D-ala2-Metenkephalinamide blocks the synaptically elicited cortical spreading depression in rats

Summary Spreading depression (SD) was elicited in rats anesthetized with pentobarbital by a train of 8 electrical pulses (0.1 ms, 10 Hz) applied to parietal cortex. Local application of 50 g of D-ala²-metenkephalinamide (DAME) on the stimulated area evoked one or two SD waves followed by an increase of SD threshold from 40 V to 90 V. This effect could be partly prevented by naloxone (1 mg/kg i.p.) and reversed by local application of 4-aminopyridine (10^–3 M, 2 l), which reduced SD threshold to 5 and 20 V in normal and DAME-treated cortex, respectively. It is argued that DAME exerts an inhibitory effect on cortical neurons and that the initial SD facilitation is due to initial blockade of inhibitory neurons in the superficial cortical layers.supported by the European Training Program in Brain and Behavior Research.     

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.     

Leishmania donovani in hamsters: Stimulation of non-specific resistance by novel lipopeptides and their effect in antileishmanial therapy

Several novel type of lipopeptides were synthesized and evaluated for their ability to stimulate non-specific resistance againstLeishmania donovani infection. Peritoneal macrophages isolated from young male hamsters treated with muramyl dipeptide (MDP) and various synthetic lipopeptides (6 mg/kg i.p.) 7 days earlier, were cultured in vitro and challenged 24 h later withL. donovani promastigotes. One lipopeptide, Central Drug Research Institute (CDRI) compound 86/450, exhibited significantly higher immunostimulatory activity than MDP. Its prophylactic activity was further confirmed in hamsters by giving 2 split doses of 3 mg/kg of the compound spaced at 2 weeks, i.e. on day –7 and +7 of challenge withL. donovani amastigotes. The prophylactic effect lasted for 7 days following the last treatment with compound 86/450. The antileishmanial action of sodium stibogluconate (SAG) was also found to be enhanced by 16% in hamsters primed with compound 86/450.CDRI Communication No. 5034.     

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.     

Inhibition of food intake in the rat by cyproheptadine

Summary In a model of conditioned feeding behavior, oral administration of cyproheptadine (1–100 mg/kg), 30 min before presentation of food, produced a dose-dependent reduction of food intake in the rat (ED₅₀17 mg/kg during the 1st h of testing). This anorexic effect persisted for at least 24 h. These results provide further evidence that under certain conditions cyproheptadine, which is used as an orectic agent in man, can produce anorexia.     

Décharge catalytique du proton en présence de séléno-cystine et de nickel

Summary It has been found that seleno-cystine, reduced to seleno-cysteine and bound in ligand form to nickel ion, produces catalytic hydrogen discharge in slight acid media. This discharge occurs in the region of a catalytic prewave located at more positive potentials (E_1/2=–1.14 V, S.C.E.) compared with the normal wave of H₃O+(E_1/2=–1,67 V, S.C.E.).     

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).     

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.     

Baclofen prevents rapid amygdala kindling in adult rats

This study investigates the effect of the gamma-aminobutyric acid (GABA_B) agonist, baclofen, on amygdala kindling in adult rats. Baclofen has been reported to be anticonvulsant in a variety of seizure models and prevents kindling in immature rats. These experiments describe the effects of baclofen (2, 5 and 10 mg/kg, i.p.) on the afterdischarge threshold and kindling rate. Baclofen, 10 mg/kg, significantly increased the afterdischarge threshold in the amygdala. Baclofen at 5 and 10 mg/kg, retarded the rate of kindling as measured by the number of stimuli required to advance to subsequent seizure stages. These results suggest that baclofen may decrease the local excitability of the amygdala and retard the rate of seizure spread (or generalization) throughout the brain. Baclofen, acting at GABA_B receptors exerts an anticonvulsant effect on amygdala kindling in these experiments.     

Methyleugenol as a surgical anesthetic in rodents

Summary Methyleugenol, suspended in Tween-80 or cremophor EL, at the dose 200–275 mg/kg i.p., is a safe anesthetic agent in rats and mice submitted to surgical procedures in the brain, without some of the inconvenience of sodium pentobarbital.     

Bilaterale Projektion der Netzhaut auf die Sehrinde des Kaninchens

Summary The bilateral representation of the retina on the visual cortex was investigated by analysing the amplitude, latency and topic distribution of the potentials evoked in the visual cortex by monocular photic stimulation of the retina in the conscious rabbit. The amplitudes of the potentials evoked on both ipsi- and contralateral hemispheres, show a relation 1:4. A small field for bilateral retinal projection of the retina was mapped in the anterolateral part of the visual cortex. These differences in amplitude, latency and topic distribution may be significant for stereoscopic vision.     

Enhancement of ethanol-induced sleep by whole oil of nutmeg

Summary In young chickens, the whole oil of nutmeg (200 mg/kg) increased the duration of sleep induced by ethanol (1–4 g/kg), particularly deep sleep. Inproniazid (50–400 mg/kg), a monoamine oxidase inhibitor, did not mimic this effect.Acknowledgments. The authors would like to thank Mr E.J. Spellman of Frische-D & O for supplying the oil of nutmeg and Mrs N. Sherry for secretarial and editorial assistance.     

In vivo effects of epinephrine in a freshwater fish

Summary In vivo effects of epinephrine were investigated in a freshwater teleost,Barbus conchonius Hamilton. Fish given 2 mg/kg epinephrine in a single i.m. dose showed significant hypocholesterolemia and elevated, liver and kidney cholesterol levels 1–8 h postinjection. Plasma amino nitrogen evinced a transient yet significant fall at 2 h followed by a significant increase after 24 h. A marked reduction occurred in the plasma FFA and organic PO₄ levels after 1–8 h. The results offer little evidence for a lipolytic effect of epinephrine in this species, and the changes in metabolite levels are attributable, in part, to the catecholamineinduced modification of insulin secretion.N.K. thanks the U.G.C. for the award of a research fellowship.     

The COMT inhibitor tolcapone potentiates the anticataleptic effect of Madopar in MPP+-lesioned mice

Orally administered Madopar (levodopa/benserazide 41) dose-dependently antagonized haloperidol-induced (1 mg/kg s.c.) catalepsy in MPP⁺-lesioned mice. Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o.), slightly potentiated the antagonistic effect of Madopar (15 mg/kg p.o.) on haloperidol-induced catalepsy. The ability of tolcapone to increase the Madopar effect was significantly attenuated by high doses of 3-O-methyldopa (3-OMD) (800 mg/kg i.p.). This might suggest a competitive blockade of the active transport of levodopa through the blood-brain barrier. In conclusion, the inhibitory effect of tolcapone on the O-methylation of levodopa to 3-OMD by COMT is largely due to improved levodopa and dopamine availability in the brain, and to the reduced formation of 3-OMD.