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EEG effects of IV infusion of pentylenetetrazol in rats: A model for screening and classifying antiepileptic compounds

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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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Faingold CL, Berry CA (1973) Quantitative evaluation of the pentylenetetrazol-anticonvulsant interaction on the EEG of the cat. Eur J Pharmacol 24:381–388

    Google Scholar 

  • Gastaut H (1970) Propriétés antiépileptiques exceptionnelles d'une benzodiazépine nouvelle. Vie Med 38:5175–5188

    Google Scholar 

  • 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

    Google Scholar 

  • Greenblatt DJ, Shader RI (1974) Benzodiazepines in clinical practice. Raven Press, New York

    Google Scholar 

  • Itil TM, Menon GN, Itil KZ (1982) Computer EEG drug data base in psychopharmacology and in drug development. Psychopharmacol Bull 18:165–172

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Pisani F, Di Perri R (1980) Some clinical pharmacological aspects of n-dipropylacetamide. Ital J Neurol Sci 4:245–249

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

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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

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