Abstract
An inverse benzodiazepine receptor agonist Ro 19-4603, administered intraperitoneally, was found to induce two types of motor seizures, i.e. minimal, predominantly clonic and major, generalized tonic-clonic, in rats at all developmental stages studied (7, 12, 18 and 25 days old). The developmental profile of the two types of seizure was different. Minimal seizures could be induced easily in the two youngest groups, whereas there were no marked differences in the induction of major seizures between the age groups. A lethal outcome was more common in 18- and 25-day-old rats than in younger animals. The convulsant action of the benzodiazepine agonist/inverse agonist Ro 19-4603 shows only quantitative changes during post-natal development in the rat.
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Abbreviations
- DPPC:
-
Diplamitoylphosphat
References
Braestrup C, Nielsen M (1978) Ontogenetic development of benzodiazepine receptors in the rat brain. Brain Res 147:170–173
Browning RA (1985) Role of the brain-stem reticular formation in tonic-clonic seizures: Lesion and pharmacological studies. Fed Proc 44:2425–2431
Browning RA, Nelson DK (1985) Variation in threshold and pattern of electroshock-induced seizures in rats depending on site of stimulation. Life Sci 37:2205–2211
Browning RA, Nelson DK (1986) Modification of electroshock and pentylenetetrazol seizure patterns in rats after precollicular transections. Exp Neurol 93:546–556
Candy JM, Martin IL (1979) The postnatal development of benzodiazepine receptor in the cerebral cortex and cerebellum of the rat. J Neurochem 32:655–658
Cavalheiro EA, Bortolotto Z, Turski L, Calderazzo Filho LS (1987) Ontogenetic aspects of beta-CCM induced convulsions. Neuroscience 22 [Suppl]:S237
Engel J Jr (1989) Seizures and Epilepsy. FA Davis Co, Philadelphia
Engelhardt E, Esbérard CA (1968) Maturation of somatomotor responses to strychnine in the albino rat. Br J Pharmacol 34:239–247
Heineman U, Jones RSG (1990) Neurophysiology. In: Dam M, Gram L (eds) Comprehensive Epileptology. Raven Press, New York, pp 17–42
Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Statist 6:56–70
Klepner CA, Lippa AS, Benson DI, Sano MC, Beer B (1979) Resolution of two biochemically and pharmacologically distinct benzodiazepine receptors. Pharmacol Biochem Behav 11:457–462
Kubová H, Mareš P (1989) Time course of the anticonvulsant action of clonazepam in developing rats. Arch Int Pharmacodyn Ther 298:15–24
Kubová H, Mareš P (1992) The effect of ontogenetic development on the anticonvulsant activity of midazolam. Life Sci 50:1665–1672
Lippa AS, Beer B, Sano M, Vogel RA, Meyerson LR (1981) Differential ontogeny of type 1 and type 2 benzodiazepine receptors. Life Sci 28:2343–2347
Löscher W, Schmidt D (1988) Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res 2:145–181
Mareš P (1991) Epileptic phenomena in the immature brain. Physiol Res 40:577–584
Mareš P, Velíšek L (1992) N-methyl-d-aspartate (NMDA)-induced seizures in developing rats. Dev Brain Res 65:185–189
Meldrum BS (1975) Epilepsy and gamma-aminobutyric acid mediated inhibition. Int Rev Neurobiol 17:1–36
Pieri L (1988) Ro 19-4603: A benzodiazepine receptor partial inverse agonist with prolonged proconvulsant action in rodents. Br J Pharmacol 95 [Suppl]:477P
Pohl M, Mareš P (1987) Flunarizine influences metrazol-induced seizures in developing rats. Epilepsy Res 1:302–305
Prichett DB, Lüddens H, Seeburg PH (1989) Type I and type II GABAA-benzodiazepine receptors produced in transfected cells. Science 245:1389–1392
Schickerová R, Mares P, Trojan S (1984) Correlation between electrocorticographic and motor phenomena induced by metrazol during ontogenesis in rats. Exp Neurol 84:153–164
Schweri MM, Martin JV, Mendelson WB, Barrett JE, Paul SM, Skolnick P (1983) Pharmacokinetic and pharmacodynamic factors contributing to the convulsant action of β-carboline-3-carboxylic acid esters. Life Sci 33:1505–1510
Sieghart W (1983) Several new benzodiazepines selectively interact with a benzodiazepine receptor subtype. Neurosci Lett 38:73–78
Swinyard EA (1973) Assay of antiepileptic drug activity in experimental animals. In: Mercier J (ed) International encyclopedia of pharmacology and therapeutics, vol. 1, Pergamon Press, Oxford, pp 47–65
Wong G, Skolnick P (1992) High affinity ligands for “diazepam-insensitive” benzodiazepine receptors. Eur J Pharmacol 225:63–68
Woodbury DM (1980) Convulsant drugs: Mechanisms of action. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs. Mechanisms of action. Raven Press, New York, pp 249–303
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Kubová, H., Mareš, P. Convulsant action of a benzodiazepine receptor agonist/inverse agonist Ro 19-4603 in developing rats. Naunyn-Schmiedeberg's Arch Pharmacol 350, 393–397 (1994). https://doi.org/10.1007/BF00178957
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DOI: https://doi.org/10.1007/BF00178957