Pharmacology of antiepileptic drugs in the gerbil—I. Pharmacokinetics

Frey, H.‐H.; Löscher, Wolfgang; Reiche, R.; Schultz, David

doi:10.1016/0028-3908(81)90227-6

Cited by 9 publications

(3 citation statements)

References 6 publications

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“…In a previous study in this species, we had determined the pharma cokinetic data for a series of commonly used antiepileptic drugs [Frey et al, 1981], In the present study, the anticonvulsant potency of these drugs was determined against 'minor' and 'major' seizures. Until now, drug actions have only sporadically been studied in gerbils [Thiessen et al, 1968;Goldblatt et al.…”

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Anticonvulsant Potency of Common Antiepileptic Drugs in the Gerbil

Frey¹,

Löscher²,

Reiche³

et al. 1983

Pharmacology

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In gerbils, ‘minor’ (myoclonic) and ‘major’ (clonictonic) seizures were induced by blowing at the animals with compressed air. The anticonvulsant ED₅₀ of the following drugs was determined after oral administration against both types of seizures: phenytoin, phenobarbital, carbamazepine, sodium valproate, ethosuximide, and diazepam. Valproate, ethosuximide, and diazepam were most potent against ‘minor’ seizures which could not or only partially be suppressed by phenytoin or carbamazepine, respectively. The ‘grand maΓ drugs phenytoin, phenobarbital, and carbamazepine were, on the other hand, more potent against ‘major’ than against ‘minor’ seizures. When phenobarbital was administered for several days, a strong induction of hepatic microsomal enzymes occurred.

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confidence: 99%

Anticonvulsant Potency of Common Antiepileptic Drugs in the Gerbil

Frey¹,

Löscher²,

Reiche³

et al. 1983

Pharmacology

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“…We now report that the drug given over a similar period adversely influences reproductive function, development and growth in the Mongolian gerbil, while having no apparent effect when given from the time of weaning. The gerbil, with its susceptibility to handling-induced seizures (Loskota et al 1972;Frey et al 1981), was selected as an appropriate alternative species. The reported half-life of phenobarbitone is 10.6 h in the gerbil (Frey et al 1981).…”

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confidence: 99%

“…The gerbil, with its susceptibility to handling-induced seizures (Loskota et al 1972;Frey et al 1981), was selected as an appropriate alternative species. The reported half-life of phenobarbitone is 10.6 h in the gerbil (Frey et al 1981). The dose selected was below the ataxic level and within the range reported to inhibit seizure activity (Goldblatt et al 1971).…”

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confidence: 99%

Phenobarbitone: adverse effects on reproductive performance and offspring development in the Mongolian gerbil, (Meriones unguiculatus)

Chapman

Cutler

1988

Psychopharmacology

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Phenobarbitone at a concentration of 500 mg/l in drinking fluid of gerbils during pregnancy (60 mg/kg) and lactation (136 mg/kg) markedly reduced the proportion of animals bearing litters, decreased pup weights at birth and during later life and delayed development of the self-righting reflex, auditory startle reaction, eye opening and full fur coverage. It also prolonged the period of suckling. Scars of implantation were evident in uterine horns of 60% of treated and in none of control females that had failed to give birth. Treated offspring after weaning were given phenobarbitone (500 mg/l; 42-124 mg/kg) as their drinking fluid throughout life and a further group of gerbils received this concentration of the drug from the time of weaning. Seizure susceptibility was unaltered by the drug treatment, and the only evidence of behavioural change was seen in offspring gerbils at 6 weeks when the bout length of social investigation during encounters was increased. Drug-treated offspring showed no abnormality in brain weight relative to body weight. Weight gain and brain weight remained normal among the gerbils given phenobarbitone after weaning. The drug treatment reduced scent gland size in breeding males, though not in the offspring, and had no effect on weights of the testes or ovaries and uterus. no effect on weights of the testes or ovaries and uterus. Plasma concentrations of phenobarbitone in females of the postweaning group amounted on average to 4.4 mg/kg. Most of the adverse effects of this dose of phenobarbitone in the gerbil can thus be seen to be associated either with reproductive impairment or with exposure during sensitive periods of early development.

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Gamma-Aminobutyric Acid (GABA)

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Molecular Orbital Calculations for Amino Acids and Peptides

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Pharmacology of antiepileptic drugs in the gerbil—I. Pharmacokinetics

Cited by 9 publications

References 6 publications

Anticonvulsant Potency of Common Antiepileptic Drugs in the Gerbil

Anticonvulsant Potency of Common Antiepileptic Drugs in the Gerbil

Phenobarbitone: adverse effects on reproductive performance and offspring development in the Mongolian gerbil, (Meriones unguiculatus)

Gamma-Aminobutyric Acid (GABA)

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