Abstract
A number of widely different animal seizure models have been employed in the search for new and novel anticonvulsant drugs useful for the tratment of human epilepsy. At present, no single laboratory test will, in itself, establish the presence or absence of anticonvulsant activity or fully predict the clinical potential of a test substance. Of the many available animal models, the maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests still represent the most commonly employed models for the routine screening and identification of new, anticonvulsant drugs. This chapter will briefly describe how these two tests are conducted, their limitations and how they have contributed in the past and to the present day anticonvulsant drug discovery process.
Sommario
Numerosi modelli animali di crisi epilettiche sono stati impiegati per ricercare nuovi farmaci antiepilettici utili per il trattamento delle epilessie umane. Attualmente nessuno dei tests di laboratorio è in grado, da solo, di stabilire il valore entiepilettico di una determinata sostanza, o di predirne l'utilità clinica. Tra i molti modelli animali disponibili quelli più comunemente impiegati per selezionare nuovi farmaci antiepilettici sono il test di risposta all'elettroshock massimale (MES) e alla somministrazione subcutanea di pentilenetetrazolo (scPTZ). Il presente capitolo passa in rassegna la metodologia dei due tests, le loro limitazioni e il contributo che essi hanno formito in passato e tutt'ora forniscono alla scoperta di nuovi farmaci antiepilettici.
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References
Everett G.M., Richards R.K.:Comparative anticonvulsive action of 3,5,5-trimethyloxazolidine-2,4-dione (Tridione), Dilantin and phenobarbital. J. Pharmacol. Exp. Ther., 81: 402–407, 1944.
Goldstein H.H., Weinberg J.:Experimental evidence of anticonvulsant properties of sodium diphenyl hydantoinate (Dilantin sodium N-N.R.) Arch. Neurol. Psychiat., 43: 453–455, 1940.
Goodman L.S., Swinyard E.A., Toman J.E.P.:Laboratory technics for the identification and evaluation of potentially antiepileptic drugs Proc. Am. Fed., Clin. Res. 2: 100–101, 1945.
Kaufman I.C., Marshall C., Walter A.E.:Metrazol activated electroencephalography. Res. Publ. Ass. Nerv. Ment. Dis. 21: 476–486, 1947.
Krall R.L., Penry J.K., Kupferberg H.J., Swinyard E.A.:Antiepileptic drug development: I. History and a program for progress. Epilepsia 19: 393–408, 1978.
Krall R.L., Penry J.K., White B.G., Kupferberg H.J., Swinyard E.A.:Antiepileptic drug development: II. Anticonvulsant drug screening. Epilepsia 19: 409–428, 1978.
Lennox W.G.:The petit mal epilepsies. Their treatment with Tridione. J.A.M.A. 129: 1069–1074, 1945.
Loscher W., Schmidt D.:Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical consideration. Epilepsy Res. 2: 145–181, 1988.
Loscher W., Fassbender C.P., Nolting B.:The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models. Epilepsy Res. 8: 79–94, 1991.
Loscher W., Honack D., Fassbender C.P., Nolting B.:The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. III. Pentylenetetrazol seizure models. Epilepsy Res. 8: 171–189, 1991.
Macdonald R.L., Kelly K.M.:Mechanisms of action of currently prescribed and newly developed antiepileptic drugs. Epilepsia 35 (S4): S41-S50, 1994.
Orlof M.J., Williams H.L. Pfeiffer C.C.:Times intravenous infusion of Metraxol and strychine for testing anticonvulsant drugs. Proc. Soc. Exp. Biol. Med. 70: 254–257, 1949.
Piredda S.G., Woodhead J.H., Swinyard E.A.:Effect of stimulus intensity on the profile of anticonvulsant activity of phenytoin, ethosuximide and valproate. J. Pharmacol. Exp. Ther 232: 741–745, 1985.
Putnam T.J., Merritt H.H.:Experimental determination of the anticonvulsant properties of some phenyl derivatives. Science 85: 525–526, 1937.
Swinyard E.A.:Laboratory evaluation of antiepileptic drugs. Epilepsia, 10:107–119, 1969.
Swinyard E.A., Brown W.C., Goodman L.S.:Comparative assays of antiepileptic drugs in mice and rats. 1952. J. Pharmacol. Exp. Ther. 106: 319–330, 1952.
Swinyard E.A., Woodhead J.H., White H.S., Franklin M.R.:General principles. Experimental selection, quantification, and evaluation of anticonvulsants, in: Levy, R. Mattson, R. Meldrum, B. Penry, J.K. and Dreifuss F.E. (eds.), Antiepileptic Drugs, Third Edition, Raven Press, Ltd., New York, pp. 85–102, 1989.
Toman J.E.P., Loewe S., Goodman L.S.:Physiology and therapy of convulsive disorders. I. Effect of anticonvulsant drugs on electroshock seizures in man. Arch. of Neurol. Psychiat. 58: 312–324, 1947.
Woodbury D.M.:Applications to drug evaluations. In Purpura D.P., Penry J.K., Tower, D., Woodbury D.M. and Walter R. (eds), Experimental Models of Epilepsy-A Manual for the Laboratory Worker, Raven Press, Ltd., New York, pp. 557–583, 1972.
Woodbury D.M., Esplin D.W.:Neuropharmacology and neurochemistry of anticonvulsant drugs. Proceedings of the Assoc. for Research in Nervous Mental Disease 37: 24–56, 1959.
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White, H.S., Johnson, M., Wolf, H.H. et al. The early identification of anticonvulsant activity: role of the maximal electroshock and subcutaneous pentylenetetrazol seizure models. Ital J Neuro Sci 16, 73–77 (1995). https://doi.org/10.1007/BF02229077
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DOI: https://doi.org/10.1007/BF02229077