Antidermatophytic action of new 1-naphthylmethyl and benzo[b]thiophen-7-ylmethyl hydrazones related to inhibitors of squalene epoxidase.

Two series of hydrazonic compounds related to main classes of inhibitors of fungal squalene epoxidase (SE) were designed and prepared on the hypothesis of a pharmacophoric model. The antifungal activity of the new compounds was evaluated in vitro against dermatophytes, moulds and yeasts. Antidermatophytic activity resulted for several hydrazones, particularly for those containing a tett-butylacetylenic group, supporting the hypothesis that the introduction of a hydrazonic function in the model could retain the antimycotic activity.

Olfactory influence on tongue activity.

Recent findings have shown that olfactory stimulation by brief puffs of air odorized with amyl acetate induces several patterns of response in rabbit hypoglossal neurons. It has been argued that the functional role of the olfactory input may be the modulation of tongue muscular tone during the oral phase of digestion. In the present research, the peripheral effect of olfactory-hypoglossal modulation was analyzed. Both the spike traffic along the fibers of the hypoglossal nerve and the electromyographic activity of single tongue muscles (genioglossus, styloglossus, superior longitudinal and hyoglossus) were recorded before, during and after olfactory stimulation. Results showed that brief puffs of air odorized with amyl acetate induced a significant change in the efferent volleys along the hypoglossal nerve, as well as a substantial modulation of tongue muscle activity. Olfactory stimulation induced a significant increase in the spontaneous activity of both type I and type II genioglossal fibers; excitation followed by inhibition both in tonic and phasic styloglossal fibers; excitatory responses in tonic and phasic superior longitudinal fibers and short-lasting excitatory responses in the hyoglossal fibers. The diverse patterns of activation of the tested muscle and the significant differences between fibers, tonically or phasically controlled by the XIIth neurons, indicate that olfaction may be strongly involved in tongue reflex regulation. Different functional hypothesis are discussed about the role played by olfaction in the economy of tongue muscle activity.

Antiepileptic treatment and oculomotor neurons.

This report describes the changes of the spontaneous firing rate due to an acute non-toxic dose of phenytoin (PHT), a drug commonly used in antiepileptic therapy, in the pre-motor neurons involved in saccadic movement. The drug (500 mg/kg of a 10% PHT suspension in arabic gum) was orally administered, and plasma and brain levels were regularly evaluated (EMIT assay). Results show that PHT significantly modifies the spontaneous electrical activity of the pre-motor neurons localized in the paramedian pontine reticular formation by inducing excitation, inhibition, or a biphasic effect. PHT action was observed 10-15 min after drug administration, when plasma and brain concentrations were still very low. The oculomotor system neurons appear to be a more specific target to this drug in comparison to the cerebellum and the vestibular system. Since the PHT action was observed 1 hour after drug administration in the vestibular nuclei and the cerebellum, which are extensively connected with the oculomotor neurons, it is possible to hypothesize that PHT can affect the oculomotor neurons directly and, with longer latency, indirectly through the vestibular nuclei and the cerebellum.

Brain electrobiogenesis protection induced by nimodipine and MK-801 during acute hypoxia in hypertensive rats.

The protective effect of nimodipine, a calcium entry blocker, and MK-801, an excitatory amino acid antagonist, on the cortical electrobiogenesis of hypertensive SHR-Charles-River adult rats during a 90-s session of acute hypoxia, was tested either with a single treatment or with a therapeutic association. Pretreatment with nimodipine alone (0.1 mg kg-1, i.v.) was particularly effective in increasing the rat brain resistence to hypoxia when compared to the controls. MK-801 pretreatment alone (3 mg kg-1, subcutaneous), improved significantly the recovery of brain electrical activity from hypoxia, as it not only shortened the recovery time but also abolished the post-hypoxic burst activity. The combined pretreatment with both drugs, using the same doses, displayed a more powerful brain protective effect on the cortical electrobiogenesis than the single drug pretreatment, suggesting the existence of a synergy between nimodipine and MK-801.

Effect of fetal hypoxia on seizure susceptibility in rats.

In the present study, susceptibility to Pentylentetrazol (PTZ)-induced seizures was tested in 45 four-wk old rats born to mothers exposed to moderate asphyxia in the last week of pregnancy by breathing N2 99.9% for 6 min in two separate sessions, (Group I--experimental rats) and in 44 rats of the same age, born after a normal pregnancy (Group II--controls). The results showed that the experimental rats, following episodes of asphyxia in intrauterine life, had a higher susceptibility to PTZ-induced seizures than the controls, manifested by earlier onset of convulsions and a higher incidence of fetal epileptic status. This occurred despite normal development and the absence of neurological deficits in the experimental rats in the first 4 wk of extrauterine life.

Cerebellar and mesencephalic influence on bulbar penicillin-G epileptogenesis in rats.

The influence of the cerebellum and mesencephalon on epileptic bulbar discharge induced by topical application of penicillin-G on the floor of the IVth ventricle was analyzed in rats. Bulbar multiunit activity was recorded at different depths. The animals were divided into two main groups: totally cerebellectomized rats (Group I) and lobus anterior cerebellectomized rats (Group II). Each main group was further subdivided into two subgroups: animals with intact mesencephalon and animals with transected mesencephalon. In Group I: the total cerebellectomy, in intact mesencephalic rats (first subgroup) induced a sudden disappearance of bulbar epileptic discharge. The mid-collicular transection (second subgroup) produced the immediate disappearance of bulbar paroxysms and the total cerebellectomy, subsequently performed, further decreased the spontaneous firing rate. In Group II: (first subgroup) the lobus anterior ablation in rats with intact mesencephalon, significantly enhanced the paroxysmal discharge. In the second subgroup, where the midcollicular transection had provoked the disappearance of bulbar paroxysms, the lobus anterior ablation induced the immediate reappearance of the paroxysmal activity. The penicillin-G epileptogenic activity showed a different intensity at different depths in the bulb with a maximum intensity at the level of the vestibular nuclei. In conclusion, the present study shows that both the mesencephalon and the cerebellum have a facilitating influence on bulbar epileptic discharge induced by the topical application of the GABA antagonist. However, not all the cerebellum has a facilitating effect, because the anterior lobus was found to have an inhibitory influence on bulbar discharge.(ABSTRACT TRUNCATED AT 250 WORDS)