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At least 289 records · Page 16Linked to original sources
PubMed1982

Development of pentazol (metrazol) activation of spontaneous motility in chick embryos.

The effect of pentazol (100 mg.kg-1 egg weight) on the spontaneous motility of normal and spinal chick embryos was studied from the 11th to the 19th day of incubation. Pentazol already activated embryonal motility, with two maxima, in 11-day embryos. Subsequent development was chiefly quantitative, especially in the first activation maximum. From the 15th day of incubation supraspinal compartments of the CNS participated significantly in pentazol activation. After the 15th day pentazol activation of spontaneous motility was inhibited by glycine- and GABA-ergic factors. The results before and after the 15th day of incubation are evaluated from the aspect of the mechanism of the action of pentazol on the central motor apparatus during embryonal maturation of the CNS.

Animals↗
PubMed1993

Effects of alprazolam on a model of human absences--rhythmic metrazol activity in rats.

Two doses of alprazolam (0.1 and 0.5 mg.kg-1) were tested against a model of human absences--rhythmic EEG activity elicited by low doses of pentylenetetrazol (35 mg.kg-1)--in 10 unrestrained rats with implanted cortical electrodes. Alprazolam delayed the onset of epileptic EEG activity, decreased the number of rhythmic episodes and shortened the total duration of rhythmic activity in a dose-dependent manner. The average duration of episodes of rhythmic activity remained unchanged; other benzodiazepines studied previously were able to influence this measure.

Alprazolam↗
PubMed1985

Convulsive thresholds in mice: action of 6-hydroxydopamine and eboracin.

The neurotoxin, 6-hydroxydopamine, when injected intraperitoneally, protected mice from seizures induced by pentylenetetrazol (Metrazol) and altered the nature of the convulsive response induced by an auditory stimulus. Conversely, the indenopyrrole, eboracin, protected mice from seizures induced by auditory stimulation and altered the response to Metrazol. In each case the altered response was characterized by a marked prolongation of the clonic component without progression to the generalized tonic phase. It appeared, therefore, that 6-hydroxydopamine raised the threshold to tonus in audiogenic seizures, and eboracin raised it in Metrazol seizures. Eboracin raised threshold to clonic phase in audiogenic seizures whereas 6-hydroxydopamine raised it in Metrazol seizures. Our findings showed that in Metrazol and audiogenic seizures thresholds to clonus and progression to the tonic phase were mediated by different biochemical mechanisms and suggested that agents controlling induction of clonic manifestations in one seizure model may be those involved in controlling seizure spread in the other.

Acoustic Stimulation↗
PubMed1976

Characteristics of pentobarbital discrimination in the gerbil: transfer and antagonism.

Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED50 of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED50: 8.5-9.6 mg/kg) and metrazol (ED50:24.9-27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100-1000 mg/kg) did not upset P-barb. discrimination. Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb, solely. Gerbils trained without a drug s-imulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2.

Animals↗
PubMed1992

The effect of ontogenetic development on the anticonvulsant activity of midazolam.

The anticonvulsant effects and duration of protective action of midazolam against Metrazol induced seizures were studied in 528 rats aged 7,12,18,25 and 90 days. The doses of 0.025, 0.05, 0.25, 0.5 and 1.0 mg/kg were administered immediately before Metrazol (100 mg/kg in all but 18-day-old animals where 90 mg/kg were given) for detection of antimetrazol activity at all age groups. The doses of 0.05, 0.25, and/or 0.5 mg/kg were used to study the time course of the protective action of midazolam. Each experimental group consisted of eight animals. Dose-dependent antimetrazol effects of midazolam till now described only in adult animals were demonstrated at all developmental stages studied. There were no qualitative differences in these effects among age groups studied. Midazolam action was better expressed against major Metrazol seizures than against minimal Metrazol seizures. Duration of the protective action depended on the dose tested at all developmental stages, as a rule, lasted longer in young animals than in adult rats. Only quantitative changes of action were found.

Animals↗
PubMedDate not supplied

Time course of the anticonvulsant action of clonazepam during ontogenesis in the rat.

A time course of the protective action of clonazepam against metrazol-induced seizures was studied in 612 rats aged 7, 12, 18, 25 and 90 days. Two doses of clonazepam (0.1 and/or 1 mg/kg) were used and metrazol (100 mg/kg in all but 18-day-old animals where 90 mg/kg were given) was administered s.c. from 30 min to 48 hr. Not all time intervals were examined in all age groups. Eight to 14 rats were used for each time interval, dose and age group. Both doses exhibited a clear-cut antimetrazol action at all developmental stages studied. The protective action lasted longest in the 2 youngest groups and shortened progressively with age. The lower dose of clonazepam always exhibited shorter duration of action than the 1 mg/kg dose. Both doses were more efficient against major than against minimal metrazol seizures in 18-day-old and older rats where minimal seizures could be reliably elicited by metrazol.

Aging↗
PubMed1996

Neural stimulation of Egr-1 messenger RNA expression in rat adrenal gland: possible relation to phenylethanolamine N-methyltransferase gene regulation.

Metrazole, which reflexively activates the splanchnic nerve to the adrenal medulla, was used to investigate the physiological role of Egr-1 in the neural regulation of phenylethanolamine N-methyltransferase (PNMT) gene transcription in the rat adrenal gland. A single dose of this drug (70 mg/kg s.c.) rapidly and transiently induced Egr-1 mRNA, with a maximum 22.0-fold increase at 30 min after treatment, followed by a 3.7-fold increase in PNMT mRNA at 8 hr. In contrast, cocaine (15 mg/kg i.p.), which activates the hypothalamic-pituitary-adrenal axis, increased Egr-1 mRNA only 3-fold at 30 min, although it elevated PNMT mRNA comparably. Consistent with their mechanisms of activation, cocaine increased corticosterone levels 7.7-fold at 30 min, whereas metrazole modestly elevated this endogenous corticosteroid 2.5-fold. The cholinergic agonists nicotine (2 mg/kg l.p.) and muscarine (0.1 mg/kg i.p.) also elevated Egr-1 mRNA, with a peak 12- to 15-fold increase being apparent at 30 min after treatment, followed by a 1.7-to 2.0-fold rise in PNMT mRNA at 8 hr. In vitro, metrazole did not increase Egr-1 mRNA above levels observed with carbachol alone (100 microM) in PC-12-derived RS1 cells pretreated with this cholinergic agonist. Finally, splanchnic denervation partially blocked the metrazole-induced rise in Egr-1 mRNA (50% control), while having no effect on cocaine-induced changes in Egr-1 mRNA. These results provide further support for the involvement of Egr-1 in the neural regulation of PNMT gene expression in the rat adrenal gland.

Adrenal Glands↗
PubMed1979

Levels and uptake of taurine in various brain regions after drug-induced generalized convulsions.

In a study of the role of taurine in the genesis of epilepsy the effects of metrazol-induced convulsions on the uptake and distribution of taurine in the brain were measured. In vivo we found no significant uptake of taurine in the mouse brain; in rabbit brain in most areas significant taurine uptake was found. The physiological levels of taurine were much higher in mouse brain than in rabbit brain. In vivo the regional levels and the uptake of taurine were not significantly changed after generalized convulsions. Uptake in vivo was lowered in slices obtained from mice treated with metrazol. The lack of effect of metrazol convulsions on cerebral taurine in vivo indicates that further studies are needed to clarify the relationship between taurine, a putative inhibitory transmitter, and epilepsy.

Animals↗
PubMed1976

Diazepam modification of evoked and spontaneous lateral geniculate activity.

The effects of diazepam on evoked and spontaneous activity of dorsal lateral geniculate nucleus (dLGN) principal (P) and inhibtory (I) cells were examined in rats. In the majority of P cells tested both spontaneous and evoked activity were suppressed following diazepam treatment with these effects being altered little by a pentylenetetrazol (Metrazol) challenge. In two P cells, which were offresponding to photic pulse stimulation, evoked and spontaneous activity was enhanced by diazepam but again these effects were altered little by the Metrazol challenge. I cell spontaneous activity was suppressed by diazepam and augmented by the Metrazol challenge; however, post-stimulus activity was relatively unaffected by either treatment. These results were discussed in terms of support for a functional re-evaluation of the rat dLGN.

Action Potentials↗