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R D Crawford

Publications and source records attributed to R D Crawford.

At least 37 records · Page 2Linked to original sources
PubMed1985

Evidence for the pharmacological relevance of benzodiazepine receptors to anticonvulsant activity.

Each of a series of benzodiazepines was found to be effective in preventing convulsions evoked by intermittent photic stimulation of epileptic chickens. There was a high correlation between the anticonvulsant potencies (mean effective dosages) and the affinity of the agents for the putative benzodiazepine receptor as measured by displacement of [3H]diazepam from binding sites on chicken synaptosomal membranes. This correlation in a genetic model of epilepsy provides further evidence that benzodiazepines exert their anticonvulsant effects by interacting with the benzodiazepine receptor.

Animals↗
PubMed1984

Pharmacology of methyl- and propyl-beta-carbolines in a hereditary model of epilepsy.

Intravenous administration of beta-carboline-3-carboxylate methyl ester (beta-CCM) produced convulsions at small doses (0.03 mg/kg) in adult chickens, homozygous for the epileptic gene. Nonepileptic heterozygote hatchmates (carriers) did not undergo seizures at doses of 1 mg/kg, and doses of 3-5 mg/kg produced only brief myoclonic responses. The convulsant effect of beta-CCM could be prevented by pretreatment with large doses of beta-carboline-3-carboxylate propyl ester (beta-CCP). beta-Carboline-3-carboxylate methyl ester displayed a higher affinity than diazepam in displacement studies on synaptosomal membrane preparations from brains of epileptic and carrier chickens.

Animals↗
PubMed1984

Cyclic nucleotides and seizures in a hereditary model of epilepsy.

The high seizure susceptibility in epileptic fowl is due to an autosomal recessive mutation. Cyclic AMP and cyclic GMP concentrations were determined in brains from two day old epileptic chicks (homozygotes) during an inter-ictal period as well as during and following a seizure evoked by stroboscopic stimulation. The data were compared to values obtained from non-epileptic carrier chicks (heterozygotes) sacrificed in an unstimulated state or subjected to the seizure evoking stimulus. During the inter-ictal state in epileptics no abnormalities were found in cyclic nucleotide concentrations indicating that the high seizure susceptibility is not related to abnormalities of these nucleotides. Although seizure activity in epileptics was associated with reduced cyclic AMP in the optic lobes this also occurred in carrier chicks subjected to the seizure evoking stimulus. The only significant changes in cyclic GMP levels, occurring as a result of seizures in epileptics, were an increase in cyclic GMP in the cerebral hemispheres during the seizure and a decrease in the optic lobes during the postictal period.

Animals↗
PubMed1983

Febrile seizures in epileptic chicks: the effects of phenobarbital, phenytoin and valproate.

Epileptic seizures can be evoked in chicks homozygous for the epileptic seizure gene (epi, epi) by elevating their body temperature using microwave diathermy. These seizures precede and differ in motor seizure pattern from a second clonic-tonic seizure produced by hyperthermia in both epileptic and carrier (heterozygote, Epi, epi) chicks. Hyperthermia did not evoke seizures in adult epileptic chickens. Phenobarbital delayed the onset of epileptiform seizures whereas phenytoin and valproate had no effect. These data suggest that epileptic chicks may provide a suitable model for studies on febrile convulsions.

Animals↗
PubMed1978

Epileptiform seizures in domestic fowl. VII. Plasma phenytoin concentrations and anticonvulsant activity.

Acute dose-response studies with phenytoin were conducted to determine the relationship between plasma levels and anticonvulsant effect in epileptic chickens. Phenytoin produced statistically significant reductions in both the incidence and severity of seizures in photosensitive epileptic chickens when the plasma concentrations exceeded 8.15 +/- 0.89 microgram/ml. A high correlation exists between plasma phenytoin concentrations and both the reduction in incidence or severity of seizures. However, the appearance of plasma concentration dependent neurological toxicities resulted in a failure to achieve complete protection against intermittent photic stimulation induced seizures.

Animals↗
PubMed1978

Epileptiform seizures in domestic fowl. VIII. Anticonvulsant activity of primidone and its metabolites, phenobarbital and phenylethylmalonamide.

Primidone is an effective anticonvulsant against seizures induced in epileptic fowl by exposure to intermittent photic stimulation. Epileptic fowl metabolize primidone to phenobarbital. Pretreatment of epileptic fowl with SKF 525A to prevent the metabolism of primidone to phenobarbital indicated that primidone itself had anticonvulsant activity. Phenylethylmalonamide, a second metabolite of primidone, did not have anticonvulsant activity when administered at the same dose as primidone.

Animals↗
PubMed1978

Epileptiform seizures in domestic fowl. IX. Implications of the absence of anticonvulsant activity of ethosuximide in a pharmacological model of epilepsy.

Acute dose--response studies were conducted to determine if ethosuximide had anticonvulsant activity against seizures evoked by stroboscopic stimulation of epileptic fowl and to correlate the observed effects with the concentration of the drug in the plasma. Ethosuximide, in doses that produced mean plasma concentrations of 366 microgram/ml and signs of sedation, did not reduce seizure susceptibility. Twice daily administration of ethosuximide produced mean plasma concentrations of 430 microgram/ml after 36 h without affecting seizure susceptibility even in the presence of marked sedation. Previous studies have shown that epileptic fowl are sensitive to the anticonvulsant effects of phenobarbital, phenytoin, and primidone at plasma concentrations similar to those required in humans. Since ethosuximide has a high specificity against petit mal seizures in humans, the failure of ethosuximide to provide protection indicates that epileptic fowl represent a relatively specific pharmacological model for drugs effective against generalized tonic--clonic and focal cortical epilepsies in humans.

Animals↗