Factors responsible for reduced pharmacological activity in rats of pentetrazol administered orally

Vohland, H. W.; Zufelde, H.

doi:10.1007/bf00507350

Cited by 7 publications

(7 citation statements)

References 20 publications

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“…Furthermore, because we wanted to maintain subconvulsant concentrations of PTZ over a prolonged period after SE, we had to establish a suitable dosing protocol because PTZ is rapidly eliminated in rats. Elimination half‐lives previously reported for PTZ in rats are 1.9 h (Ramzan & Levy, 1985), ∼2.5 h (Esplin & Woodbury, 1956), and ∼3.5 h (Vohland & Zufelde, 1976), so the present value of 3.3 h fits well within this range. Following i.v.…”

Section: Discussionsupporting

confidence: 83%

“…6A). They declined from 11.48 μg/mL at 0.25 h to 7.4 μg/mL at 4 h with a half‐life of 5.69 h. Thus, the average half‐life of PTZ calculated from these four rats was 3.3 h, which is very similar to the 3.5 h reported by Vohland & Zufelde (1976) for female rats.…”

Section: Resultssupporting

confidence: 76%

“…An alternative explanation for the increased susceptibility to PTZ after brain insults such as SE could be impaired integrity of the blood‐brain barrier (BBB) leading to increased drug permeability (Friedman, 2011). This, however, is unlikely to affect brain penetration of PTZ, because this small lipophilic compound rapidly penetrates the BBB and reaches the same concentrations in brain and cerebrospinal fluid as in plasma following systemic administration (Vohland & Zufelde, 1976; Ramzan & Levy, 1985); the BBB does not present a barrier for this drug.…”

Section: Discussionmentioning

confidence: 99%

“…As PTZ is rapidly eliminated in rats, with a half‐life of ∼2 to 3 h (Esplin & Woodbury, 1956; Vohland & Zufelde, 1976; Ramzan & Levy, 1985), we decided to develop an i.v. infusion protocol that allows maintenance of subconvulsant concentrations of PTZ over 48 h following SE.…”

Section: Methodsmentioning

confidence: 99%

“…In preliminary experiments in controls and SE rats, blood was sampled after 24 and 48 h of infusion to determine whether the target concentration was reached and maintained. Brain levels of PTZ were not measured, because Vohland & Zufelde (1976) showed that plasma levels correspond to brain levels of PTZ in rats.…”

Section: Methodsmentioning

confidence: 99%

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Do proconvulsants modify or halt epileptogenesis? Pentylenetetrazole is ineffective in two rat models of temporal lobe epilepsy

Rattka

Brandt

Löscher

2012

Eur J of Neuroscience

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In patients at risk of developing epilepsy after an initial precipitating injury to the brain, the epileptogenic latent period may offer a window of opportunity for initiating potential antiepileptogenic therapy in an attempt to prevent epilepsy from developing. One potential target for antiepileptogenesis is the development of neuronal hyperexcitability during the latent period. Surprisingly, some recent studies in models of temporal lobe epilepsy (TLE) have suggested that proconvulsant drugs could have favourable effects on epileptogenesis, resulting in the proposal of pursuing proconvulsant prophylaxis for epileptogenesis. In the present study, we evaluated this provocative hypothesis by experiments with the GABA(A) receptor antagonist pentylenetetrazole (PTZ) in two TLE models, the intrahippocampal kainate model and the lithium-pilocarpine model in rats. First, we repeatedly determined the PTZ seizure threshold by i.v. infusion of the convulsant during the latent period following intrahippocampal kainate. In line with recent experiments in the lithium-pilocarpine model, the PTZ seizure threshold was significantly decreased over several days following status epilepticus. We then studied whether prolonged infusion of a proconvulsant dose of PTZ at different times after kainate or pilocarpine affected the development of epilepsy. PTZ did not prevent the development of spontaneous recurrent seizures and did not decrease their frequency or severity, but exerted only a moderate disease-modifying effect in that spontaneous seizures in the kainate model were significantly shortened. These data indicate that administration of proconvulsant drugs such as PTZ during the latent period following SE is not a promising strategy for preventing epilepsy.

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Section: Discussionsupporting

confidence: 83%

Section: Resultssupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Do proconvulsants modify or halt epileptogenesis? Pentylenetetrazole is ineffective in two rat models of temporal lobe epilepsy

Rattka

Brandt

Löscher

2012

Eur J of Neuroscience

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Zur Toxikologie von Carbromal

1977

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Oral doses up to 20 mg/kg of carbromal and of bromoethylbutyramide were rapidly absorbed in the rat. Absorption from the stomach ligated at the pyloric end was 5-8 fold less than absorption of carbromal injected directly into the small intestine. Oral doses greater than 20 mg/kg of carbromal disappeared more slowly from the gastro-intestinal tract because gastric emptying was delayed. Both carbromal and bromoethylbutyramide were able to reduce the basal tone and the acetylcholine-induced contraction of isolated rat fundus strips. Carbromal and bromoethylbutyramide distributed evenly between serum, brain and skeletal muscle. Concentrations in adipose tissue were three times those in the other three tissues. Concentrations of both carbromal and of bromoethylbutyramide in all four tissues declined at the same rate. Thus, serum concentration of either compound may be used to estimate the total body content. Intraperitoneally injected carbromal, bromoethylbutyramide and ethylbutyrylurea disappeared from the brain and from the serum with half-life of 3-4 h and 5-7 h, respectively. Traces only of unchanged carbromal, bromoethylbutyramide, or ethylbutyrylurea were excreted with urine or feces indicating rapid and extensive biotransformation of the three compounds in this species. No evidence was obtained of secretion of either carbromal or its two metabolites into the lumen of the stomach. The findings are discussed as to their relevance for acute carbromal poisoning in humans.

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Repeated administration of subconvulsant doses of GABA antagonist drugs

et al. 1982

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The effect on monoamine-medical behaviour of repeated daily subconvulsive doses of the GABA antagonist drugs pentylenetetrazol (PTZ) (30 mg/kg for 8 days), picrotoxin (5 mg/kg for 4 days) and bicuculline (3.5 mg/kg for 16 days) was investigated. None of the drugs, administered chronically, increased behavioural responses to the 5-hydroxytryptamine agonist quipazine (25 mg/kg), and neither picrotoxin nor bicuculline altered the locomotor response to the dopamine agonist apomorphine (AP) (0.1 mg/kg). By contrast, repeated doses of PTZ increased the locomotor response to AP, and also increased circling responses to both AP (0.5 mg/kg) and methamphetamine (2.0 mg/kg) in unilateral nigrostriatal-lesioned rats.

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Factors responsible for reduced pharmacological activity in rats of pentetrazol administered orally

Cited by 7 publications

References 20 publications

Do proconvulsants modify or halt epileptogenesis? Pentylenetetrazole is ineffective in two rat models of temporal lobe epilepsy

Do proconvulsants modify or halt epileptogenesis? Pentylenetetrazole is ineffective in two rat models of temporal lobe epilepsy

Zur Toxikologie von Carbromal

Repeated administration of subconvulsant doses of GABA antagonist drugs

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