SEARCH · PubMed Health

Results for “METRAZOL”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed1978

Metrazol-induced petit mal: the role played by monoaminergic mechanisms and striatum.

Gradually accumulating subconvulsive doses of metrazol give rise to behavioral and electrographic effects close to petit mal epilepsy: slow negative waves and spike-wave complexes on EEG, frozen and myoclonic jerks. Intensification of monoaminergic transmission with apomorphine, DOPA or 5-hydroxytryptophan attenuates, but inhibition (chlorpromazine, haloperidol and p-chlorphenylalanine), on the contrary, increases the subconvulsive effect of the metrazol. Low frequency stimulation of the striatum potentiates, and lesion limits expressiveness of metrazol-induced petit mal. Bilateral electrolytic lesion of the striatum eliminates apomorphine, DOPA and haloperidol action, but slight changes the effects of chlorpromazine, 5-hydroxytryptophan and p-chlorphenylalanine.

Animals↗

PubMed1989

Effects of ketamine on metrazol-induced seizures during ontogenesis in rats.

An anticonvulsant action of ketamine, a noncompetitive NMDA receptor antagonist (1-40 mg/kg IP), on the metrazol-induced seizures was assessed in male Wistar rats aged 7, 12, 18, 25 and 90 days. Ketamine alone caused ataxia even in the lowest dose used. As concerens its interaction with metrazol it exerted a clearcut anticonvulsant effect against generalized tonic-clonic seizures at all developmental stages. On the contrary, the effects on clonic (i.e., minimal) seizures were only moderate or absent. Higher efficacy of ketamine was observed in young animals. Our results suggest a role of excitatory amino acids in the generation of generalized tonic-clonic metrazol seizures, but their share on the induction of clonic (minimal) seizures seems to be very small.

Aging↗

PubMed1991

Effect of tyrosine on the potentiation by aspartame and phenylalanine of metrazol-induced convulsions in rats.

Male rats were treated by oral intubation with tyrosine (Tyr), at doses of 0.5 and 1.0 g/kg body weight, alone or together with 1 g aspartame (APM)/kg body weight, or an equivalent dose of phenylalanine (Phe; 0.5 g/kg body weight); the effects on seizures induced by an effective dose of metrazol (ED50) were observed. Tyr (0.5 g/kg body weight) had a protective effect against the Phe-potentiation of metrazol-induced clonic-tonic convulsions. At the same dose Tyr had no effect on the seizure-promoting activity of APM, but at 1 g/kg it reduced the proconvulsant potential of the sweetener. Analysis of the brain and plasma amino acid concentrations indicated that the Tyr to Phe ratio tended to be enhanced in Tyr-Phe treated rats compared with those treated with Phe alone. This ratio remained essentially constant in the brain of APM-treated rats, compared with those treated with APM plus 1 g Tyr/kg body weight, whereas an increase in this ratio in the plasma was observed. These results confirm that Tyr antagonizes the proconvulsant effect of Phe and APM and they further suggest that no simple relationship exists between the relative brain concentrations of the two amino acids and the response to metrazol convulsions.

Animals↗

PubMed1982

Eboracin: a substituted indenopyrrole active against metrazol-induced, audiogenic and electroshock seizures in mice.

1. Pretreatment with eboracin, a methyl ester of a trioxyindenopyrrole, inhibited the tonic phase of pentylenetetrazol (Metrazol)-induced, audiogenic and electroshock seizures in mice. 2. In animals challenged with Metrazol a dose of 28 mg/kg eboracin prevented 50% of tonic-clonic responses. 3. In animals exposed to electroshock or auditory stimulation the dose required to produce a 50% reduction in tonic-clonic seizures was 30 mg/kg and 35 mg/kg, respectively. 4. The 50% lethal dose was 832 mg/kg, indicative of eboracin's relatively low toxicity and high therapeutic index. 5. Pretreatment with eboracin led to a prolongation of the myoclonic phase of Metrazol seizures, similar to that observed after phenytoin.

Acoustic Stimulation↗

PubMed1989

The effect of monoamine depletors on metrazol induced convulsions and brain gamma-aminobutyric acid (GABA) contents in rats.

The thresholds for metrazol (pentylenetetrazol) clonic convulsions and brain gamma-aminobutyric acid contents were significantly reduced after treatment with the monoamine depletors reserpine, tetrabenazine and p-chlorophenylalanine. Moreover, alpha-methyltyrosine, and alpha-methyl-m-tyrosine also lowered metrazol threshold seizures, but had no effect on brain alpha-aminobutyric acid contents. Furthermore, neither 5-hydroxytryptophan nor tranylcypromine had a significant effect on metrazol threshold seizures or brain alpha-aminobutyric acid contents, but blocked the changes previously induced by p-chlorophenyl alanine and reserpine.

Animals↗

PubMed1981

Metrazol thresholds in inbred and non-inbred audiosensitive mice.

Mice of the O'Grady strain which were inbred for susceptibility to audiogenic seizures were found to be more sensitive to pentamethylenetetrazol (Metrazol) convulsions than mice of the parent Swiss-Webster strain from which they were originally derived. A dose of 35 mg/kg Metrazol was required to produce a 50% convulsive response (CD50) in O'Grady mice and 50 mg/kg in the control parent strain. No differences in convulsive thresholds to Metrazol were obtained, however, between untreated Swiss-Webster mice and mice of the same strain made audiosuseptible by rubidium chloride intake or magnesium deficiency.

Acoustic Stimulation↗

PubMedDate not supplied

Effects of loreclezole on metrazol-induced phenomena in developing rats.

A potential antiepileptic drug, loreclezole, was studied in rats of 7, 12, 18, 25 and 90 days old. Metrazol-induced motor phenomena served as a model. Loreclezole did not consistently influence isolated myoclonic jerks or minimal metrazol seizures (predominantly clonic with preserved righting ability). Major metrazol seizures, i.e., generalized tonic-clonic seizures, were suppressed by loreclezole in a dose-dependent manner in all age-groups, except in the 7 day old group where outlined changes did not reach statistical significance. Severity of seizures was significantly diminished at all developmental stages studied. Loreclezole exhibits nearly the same profile of action as phenytoin and carbamazepine in this model.

Animals↗

PubMed1989

Rhythmic metrazol activity in rats as a model of human absences.

Rhythmic activity of the spike-and-wave type was induced by administration of metrazol (25 or 50 mg/kg s.c.) in male rats with implanted cortical electrodes. The animals were deprived of water and then allowed to lick water from a tube. Under control conditions they licked for 3-4 min without an interruption. Rhythmic metrazol activity deranged the licking; when this pathologic activity represented about one third of the time, the licking was fully blocked. We conclude that the impairment of highly motivated behaviour confirms the adequacy of the rhythmic metrazol activity as a model of human primary generalized seizures of the absence type.

Animals↗

PubMed1987

Influence of clonazepam on electrocorticographic changes induced by metrazol in rats during ontogenesis.

The action of clonazepam (CZP) pretreatment on metrazol-induced ECoG phenomena was studied in Wistar albino rats. ECoG was recorded in acute experiments in male rats 7, 12, 18, 25 and 90 days old (N = 162). CZP (0.1 or 0.02 mg/kg) was injected i.p. 10 min prior to the start of repetitive administration of metrazol (PTZ, 20 mg/kg i.p. every 5 min). Latencies of the first signs of PTZ action, of the rhythmic metrazol activity, of the first ictal activity and of the generalized seizure were measured. CZP exhibited a dose-related effect against ECoG signs elicited by PTZ. A statistically significant increase in latencies was observed with the dose of 0.1 mg/kg in 18 day old and older animals. The 0.1 mg/kg dose of CZP also completely blocked generalized ictal activity in 7 day old rats. In adult animals, CZP pretreatment led to the appearance of partial seizures, a phenomenon never seen in controls. The development of CZP effects corresponds to the maturation of benzodiazepine binding sites.

Aging↗

PubMed1982

Influence of clonazepam and ethosuximide on ECoG pattern induced by metrazol during ontogenesis in rats.

Metrazol (80 mg/kg s. c.) elicited ECoG episodes of rhythmic activity the shape, frequency and localization of which depended on the age of rats. In 15- and 12-day-old animals there was a progression into sustained ictal activity. Clonazepam (1 mg/kg i. p.) exhibited excellent anti-metrazol action in adult, 25- and 12-day-old rats. The results in 15-day-old animals were inconsistent. Ethosuximide (125 mg/kg i. p.) protected sufficiently only adult and 25-day-old rats. In younger age groups only ictal activity was blocked, while metrazol-induced episodes remained untouched.

Age Factors↗

PubMed1980

Seizures elicited by subcutaneous injection of metrazol during ontogenesis in rats.

Metrazol administered subcutaneously at a dose of 80 mg . kg-1 elicited genuine minimal seizures (predominantly clonic) in adult, 45- and 25-day-old rats. The same dose of metrazol resulted in long-lasting generalized tonic-clonic seizures in rats aged 15 days and younger. Eighteen-day-old rats represented a transitory stage in which both types of seizures were present: minor seizures at first and then, after a short resting period, major seizures. A different seizure pattern in young rats was not induced by their higher sensitivity to metrazol, but was caused by the level of neural maturation.

Age Factors↗

PubMed1995

Differential induction of the ZENK gene in the avian forebrain and song control circuit after metrazole-induced depolarization.

ZENK is an immediate early gene (IEG) that encodes a transcription factor protein, and its induction has been proposed as a necessary step in the cellular process underlying long-term memory formation. We have previously shown that ZENK is induced in adult songbird brain by the sound of birdsong, but, interestingly, induction did not occur in several areas known to respond to song stimuli. Conceivably, the ZENK gene may be repressed in these areas in adult birds. As a further test of this hypothesis, we administered metrazole, a strong GABAergic antagonist that leads to widespread excitation in the brain. Following metrazole, ZENK mRNA increases more than 10-fold throughout most of the telencephalon in both canaries and zebra finches, and primarily in neurons. In contrast, ZENK induction is much lower or absent in the archistriatum, the primary telencephalic sensory-recipient areas (including auditory field L), and the three telencephalic androgen receptor-containing song nuclei (high vocal center, lateral magnocellular nucleus of the anterior neostriatum, and the robust nucleus of the archistriatum). We did not observe any differences in ZENK induction patterns in juvenile versus adult zebra finches, or fall versus spring male canaries. Together with our previous studies of induction by song, these results suggest that in specific parts of the forebrain, including most of the song control system, IEG expression is subject to different constraints than in the rest of the forebrain. Understanding the molecular basis for this differential gene regulation may prove invaluable in understanding the organization of the song control circuit and the avian telencephalon.

Animals↗

PubMedDate not supplied

Metrazol enhances brain penetration and therapeutic efficacy of some anticancer agents: implications for brain metastases.

The concurrent administration of Metrazol (60 mg/kg, i.v.) to anaesthetized rats enhances the cerebral penetration of the anticancer agent razoxane. Such an enhancement leads to an increase in the therapeutic efficacy of razoxane against intracerebrally sequestered L1210 leukaemia cells in mice. The combination of Metrazol and melphalan was also examined to see if the concentration of other anticancer agents in CSF could be enhanced.

Animals↗

PubMed1985

Differential antagonism of denzimol to various components of metrazol-induced seizures in rats and mice.

The antagonism of various components of maximal metrazol-seizures and the induction of ataxia have been studied in mice and rats by comparing Denzimol to 10 standard antiepileptic drugs. The data were analyzed by Cluster and Principal Components Analysis. Denzimol, phenytoin, carbamazepine and AD-810 showed an antagonistic effect on tonic but not on clonic seizures regardless of the animal species. Barbiturates, benzodiazepines and valproic acid, on the other hand, antagonized the whole pattern of metrazol-seizures. The selective activity of Denzimol and phenytoin against tonic seizures was also confirmed from literature data, which reported the activity of these compounds against bicuculline, thiosemicarbazide or picrotoxin induced convulsions.

Administration, Oral↗

PubMed1976

Dose-related effects of metrazol on retention and EEG.

The effects of various dose levels of Metrazol on retention and electrocorticogram (ECoG) were investigated. Mice given a subconvulsive 30 mg/kg or a convulsive 50 mg/kg dose of Metrazol 15 min before reversal training in a discriminated escape learning task showed retention impairment of reversal training retention. Lower dose levels (5 or 10 mg/kg) had no effect. The 30 mg/kg dose produced asymmetrical dissociation. The convulsive dose (50 mg/kg), previously reported to result in symmetrical dissociation, produced ECoG changes that were still evident 15 min following the injection, i.e. at the time when training or testing usually took place. With lower doses (10 or 30 mg/kg), no apparent ECoG effects were observed at this interval. The implications of the findings were discussed with respect to the state-dependent hypothesis.

Animals↗

PubMed1991

Interspecies and interstrain studies on the increased susceptibility to metrazol-induced convulsions in animals given aspartame.

The ability of aspartame (APM) to increase the susceptibility to metrazol-induced convulsions was studied in two strains of mice (CD1 and DBA/2J) and in guinea-pigs. Rats were included as known positive controls. Plasma and brain levels of phenylalanine (Phe) and tyrosine (Tyr) were measured in CD1 mice and guinea-pigs at various intervals after a dose of 1 g APM/kg body weight (administered orally to mice and ip to guinea-pigs). In mice, peak levels of Phe and Tyr were observed in plasma after 30 min and in brain after 60 min. In guinea-pigs peak plasma levels of Phe and Tyr occurred 30 min after treatment. Phe was at a maximum in guinea-pig brain after 30 min, while Tyr levels reached a peak at 120 min. In further experiments Phe and Tyr levels were measured 1 hr after APM doses of 0.5, 0.75 or 1 g/kg. In CD1 mice, plasma Phe and Tyr levels were increased significantly only at the highest dose, whereas in brain, Tyr concentrations were significantly increased by 0.75 or 1 g APM/kg and Phe was significantly increased by all three doses. In the guinea-pig, plasma Phe and Tyr were increased significantly only by 1 g APM/kg and in brain this dose significantly raised only the Phe levels. Monoamine and metabolite levels were determined in the brain striata of CD1 and DBA/2J mice 1 hr after the oral administration of 1 or 2 g APM/kg body weight; no differences from control values were found in either strain. The studies of potentiation of metrazol-induced convulsions showed that APM, at doses of up to 2 g/kg body weight, had no such effect in mice or guinea-pigs. In contrast, as expected, the potentiation was significant in the rat at 1 g/kg.

Animals↗

PubMed1987

Effects of flunarizine on Metrazol-induced seizures in developing rats.

Antimetrazol action of flunarizine (5, 10, 20 and 40 mg/kg i.p.) was tested during ontogenesis on male Wistar rats aged 7, 12, 18, 25 and 90 days. The latencies and incidences of jerks, minimal Metrazol seizures and major Metrazol seizures remained unchanged by flunarizine in all age groups. A specific action (an abolition of the tonic phase of major seizures) was seen throughout the development and was reflected in lower scores of seizures.

Aging↗

PubMed1992

Panoramic imaging of brain pHi and CBF during penicillin and metrazole induced status epilepticus.

Using real-time in vivo umbelliferone fluorescent imaging, cortical intracellular brain pH (pHi) and cortical blood flow (CBF) were measured in New Zealand white rabbits during generalized seizures induced by intravenous metrazole or sodium penicillin. In the former, brain pHi declined from 7.04 +/- 0.07 to 6.78 +/- 0.07 within 15 min of generalized seizures and remained at this level for 1 h. In the penicillin group, pHi fell from 7.05 +/- 0.10 to 6.81 +/- 0.07 and also remained at this level over 60 min. This brain acidosis was uniform across the brain's surface. With the onset of status epilepticus there was a hyperemia which occurred in a heterogeneous pattern with blood flow appearing to be greater adjacent to cortical vasculature and slower in border zones between surface blood vessels. In the metrazole group, there was evidence of vasomotor paralysis with loss of autoregulation involving both cortical surface vasculature and penetrating arterioles with their capillary beds.

Animals↗