Abstract
In order to validate a new animal model predictive of the profile of antiepileptic drugs, we studied the antagonism by standard antiepileptics of the EEG modifications induced by low-speed IV infusion of pentylenetetrazol (PTZ) in rats. The activity of the drugs was measured by their effects on temporal characteristics of the PTZ-induced EEG paroxysms. Most compounds had moderate to potent anti-PTZ effects, as shown by the changes in the EEG temporal parameters. However, these effects depended on the drugs and doses. Cluster analysis showed that drugs and doses which evoked similar changes were closely related and were included in separate clusters with respect to one another. In particular, the present results showed that benzodiazepines and antiepileptics cluster differently in their effects. Thus, this model could be a useful tool for assessing new antiepileptic drugs.
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References
Browne TR, Penry JK (1973) Benzodiazepines in the treatment of epilepsy. A review. Epilepsia 14:277–310
Carraz G, Lebreton S, Eymard P, Meunier H (1968) Pharmacodynamie de l'acide dipropylacetique (ou propyl-2-pentanoique) et de ses amides. Carraz G (ed) Imp. Eymond, Grenoble, France
Desmedt LKC, Niemegeers CJE, Lewi PJ, Janssen PAJ (1976) Antagonism of maximal metrazol seizures in rats and its relevance to an experimental classification of antiepileptic drugs. Arzneim Forsch 26:1592–1602
Faingold CL, Berry CA (1973) Quantitative evaluation of the pentylenetetrazol-anticonvulsant interaction on the EEG of the cat. Eur J Pharmacol 24:381–388
Gastaut H (1970) Propriétés antiépileptiques exceptionnelles d'une benzodiazépine nouvelle. Vie Med 38:5175–5188
Glaser GH (1980) Mechanisms of antiepileptic drug action: clinical indicators. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs: mechanisms of action, Raven Press, New York, pp 11–20
Greenblatt DJ, Shader RI (1974) Benzodiazepines in clinical practice. Raven Press, New York
Itil TM, Menon GN, Itil KZ (1982) Computer EEG drug data base in psychopharmacology and in drug development. Psychopharmacol Bull 18:165–172
Kent AP, Webster RA (1983) The evaluation of different types of anticonvulsant drug activity against leptazol-induced epileptogenic activity in the anaesthetized rat. Br J Pharmacol 78:553–559
Masuda Y, Shiraishi Y, Karasawa T, Yoshida K, Shimizu M (1980) Differential antagonisms of anticonvulsants to various components of maximal seizures induced by electroshock or pentylenetetrazol in mice. J Pharm Dyn 3:526–531
Pisani F, Di Perri R (1980) Some clinical pharmacological aspects of n-dipropylacetamide. Ital J Neurol Sci 4:245–249
Pisani F, Fazio A, Oteri G, Di Perri R (1981) Dipropylacetic acid plasma levels; diurnal fluctuations during chronic treatment with dipropylacetamide. Therapeutic Drug Monitoring 3:279–301
Pisani F, Fazio A, Oteri G, Di Perri R (1982) A study on the metabolism of dipropylacetamide to dipropylacetic acid in rats. J Pharm Pharmacol 34:45–46
Purpura D, Penry JK, Tower DB, Woodbury DM, Walter A (1972) Experimental models of epilepsy: A manual for the laboratory worker. Raven Press, New York
Santucci V, Fournier M, Simiand J, Keane P, Morre M (1983) Effects of dipropylacetate (DPA) on pentetrazol-induced EEG abnormalities: Relation with GABA. Third Eur Winter Conf Brain Res, 13–19 March 1983. Les Arcs, France
Simiand J, Eymard P, Ferrandes B, Polverelli M (1973) Pharmacocinétique du di-n-propylacétamide chez le rat après administration par voie buccale. Ann Pharm Fr 31:205–216
Swinyard EA, Woodhead JH (1982) Experimental detection, quantification and evaluation of anticonvulsants. In: Woodbury DM, Penry JK, Pippenger CE (eds) Antiepileptic Drugs, Raven Press, New York, pp 111–126
Testa R, Graziani L, Graziani G (1983) Do different anticonvulsant tests provide the same information concerning the profiles of antiepileptic activity? Pharmacol Res Commun 15:765–774
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Santucci, V., Fournier, M., Keane, P. et al. EEG effects of IV infusion of pentylenetetrazol in rats: A model for screening and classifying antiepileptic compounds. Psychopharmacology 87, 337–343 (1985). https://doi.org/10.1007/BF00432718
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DOI: https://doi.org/10.1007/BF00432718