Abstract
This paper develops a method to estimate a minimal amount of flurothyl necessary to induce the seizures (the seizure threshold). A simple mathematical model is proposed which permits one to determine the drug absorption rate from the amount which has been administered and from the measured latency to onset of seizure. Experimental animal (rats) were exposed to a continuous intake of flurothyl in two different situations: either being alone in the airtight chamber or sharing it in a pair. In the latter case, we assume that the two rats uniformly share the infused drug. Our calculations estimate that approximately 20 μl of flurothyl is necessary to induced twitches, whereas 25 μl of flurothyl is the dose required for the induction of clonic seizures. The model can be used to estimate the threshold amounts of any drug producing obvious behavioral changes irrespective of the route of administration.
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References
Goddard, G. V. 1967. Development of epileptic seizures through brain stimulation at low intensity.Nature 204, 1020–1021.
Holmes, G. L. 1991. The long-term effects of seizures on the developing brain: clinical and laboratory issues.Brain Dev. 13, 393–409.
Holmes, G. L., J. L. Thompson, G. F. Carl, B. S. Gallagher, J. Hoy and M. McLaughlin. 1990. Effect of 2-amino-7-phosphonoheptanoic acid (APH) on seizure susceptibility in the prepubescent and mature rat.Epilepsy Res. 5, 125–130.
Holmes, G. L., S. J. Thurber, Z. Liu, C. E. Stafström, A. Gatt and M. A. Mikati. 1993. Effects of quisqualic acid and glutamate on subsequent learning, emotionality, and seizure susceptibility in the immature and mature animal.Brain Res. 623 325–328.
Inamura, K., E. Martins, K. Themner, S. Tapper, J. Pallon, G. Lovestam, K. G. Malmqvist and B. K. Siejo. 1990. Accumulation of calcium in substatia nigra lesions induced by status epilepticus. Amicroprobe analysis.Brain Res. 514, 49–54.
Jacquez, J. A. 1985.Compartmental Analysis in Biology and Medicine, Ann Arbor: University of Michigan Press.
Jensen, F. E., I. R. Firkusny and G. D. Mower. 1993. Differences in c-fos immunoreativity due to age and mode of seizure induction.Mol. Brain. Res. 17, 185–193.
Jensen, F. E., G. L. Holmes, C. T. Lombroso, H. K. Blume and I. R. Firkusny. 1992. Age-dependent changes in long-term seizure susceptibility and behavior after hypoxia in rats.Epilepsia 33, 971–980.
Lánský, P. 1983. Inference for the diffusion models of neuronal activity.Math. Biosci. 67, 247–260.
Liu, Z., A. Gatt, S. J. Werner, M. A. Mikati and G. L. Holmes. 1994. Long-term behavioral deficits following pilocarpine seizures in immature rats.Epilepsy Res. 19, 191–204.
Löscher, W. and D. Schmidt. 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.
Lowenstein, D. H., R. P. Simon and F. R. Sharp. 1990. The pattern of 72-kDa heat shock protein-like immunoreativity in the rat brain following flurothyl-induced status epilepticus.Brain Res. 531, 173–182.
Lundgren, J., M. L. Smith, G. Blennow and B. K. Siesio, 1994. Hyperthermia aggravates and hypothermia ameliorates epileptic brain damage.Exp. Brain Res. 99, 43–55.
Nomikos, G. G., A. P. Zis, G. Damsma an H. C. Fibiger. 1994. Electroconvulsive shock increases interstitial concentrations of uric acid in the rat brain.Brain Res. 660, 50–56.
Prichard, J. W., B. B. Gallagher and G. H. Glase. 1969 Experimental seizure threshold testing with flurothyl.J. Pharm. Exp. Ther. 166, 170–178.
Ricciardi, L. M. and S. Sato. 1990. Diffusion processes and first-passage-time problems. InLectures in Applied Malthematics and Informatics, L. M. Ricciardi (Ed.) Manchester: Manchester University Press.
Sperber, E. F. and S. L. Moshé, 1988. Age-related differences in seizure susceptibility to flurothyl.Dev. Brain Res. 39, 295–297.
Stafström, C. E., G. L. Holmes and J. L. Thompson. 1993. MK801, pretreatment reduces kainic acid-induced spontaneous seizures in prepubescent rats.Epilepsy Res. 14, 41–48.
Stafström, C. E., J. L. Thompson and G. L. Holmes. 1992. Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures.Dev. Brain Res. 65, 227–236.
Stein-Behrens, B. A., W. J. Liu and R. M. Sapolsky. 1994. Physiological elevations of glucocorticoids potentiate glutamate accumulation in the hippocampus.J. Neurochem. 63, 596–602.
Terndrup, T., F. Starr and W. E. Fordyce. 1994. A piglet model of status epilepticus: comparison of cardiorespiratory and metabolic changes with two methods of pentylenetetrazol administration.Ann. Emerg. Med. 23, 470–479.
Tortella, F. C., L. Robles, E. Echavarria, J. C. Hunter and J. Hughes. 1990. PD117302, a selective non-peptide opioid kappa agonist, protects against NMDA and maximal electroshock convulsions in rats.Life Sci. 45, PL1–7.
Tortella, F. C., L. Robles, J. M. Witkin and A. H. Newman. 1994. Novel anticonvulsant analogs of dextromethorphan: improved efficacy, potency, duration and side-effect profile.J. Pharmacol. Exp. ther. 268, 727–733.
Truitt, E. B., E. M. Ebesberg and A. S. G. Ling. 1960. Measurement of brain excitability by use of hexaflurodiethyl ether (Indoclon).J. Pharm. Exp. Ther. 129, 445–453.
van Rossum, J. M., J. G. M. de Bie, G. van Lingen and H. W. A. Teeuwen. 1989. Pharmacokinetics from a dynamical system point of view.J. Pharmacokin Biopharmacol. 17, 365–397.
Velíšek, L., S. L. Moshé, S.-G. Xu and W. Cammer. 1993. Reduced susceptibility to seizures in carbonic anhydrase II deficient mutant mice.Epilepsy Res.,14, 115–121.
Velíšek, L., J. Velíšková, Y. Ptachewich, S. Shinnar and S. L. Moshé. 1995 Effects of MK801 and phenytoin on flurothyl-induced seizures during development.Epilepsia 36, 179–185.
Weiss, M. 1991. Residence time distribution in pharmacokinetics: behavioral and structural models. InAdvanced Methods in Pharmacokinetic and Pharmacodynamic Systems Analysis, D. Z. D'Argenio (Ed), pp. 89–101. New York: Plenum Press.
Xu, S.-G., D. S. Garant, E. F. Sperber and S. L. Moshé. 1992. The proconvulsant effect of nigral infusion of THIP on flurothyl-induced seizures in rat pups.Develop. Brain Res. 68, 275–277.
Young, R. S., O. A. Petroff, B. Chen, J. C. Gore and W. J. Aquila. 1991. Brain energy state and lactate metabolism during status epilepticus in the neonatal dog: in vivo 31P and 1H nuclear magnetic resonance study.Pediatr. Res. 29, 191–195.
Zhong, J., O. A. Petroff, J. W. Prichard and J. C. Gore. 1995. Barbiturate-reversible reduction of water diffusion coefficient in flurothyl-induced status epilepticus in rats.Magn. Reson. Med. 33, 253–256.
Zis, A. P., G. G. Nomikos, E. E. Brown, G. Damsma and H. C. Fibiger. 1992. Neutrochemical effects of electrically and chemically induced seizures: an in vivo microdialysis study in the rat hippocampus.Neuropsychopharmacology 7, 189–195.
Zis, A. P., G. G. Nomikos, G. Damsma and H. C. Fibiger. 1991. In vivo neurochemical effects of electroconvulsive shock studied by microdialysis in the rat striatum.Psychopharmacology (Berlin)103, 343–350.
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Lánský, P., Velíšková, J. & Velíšek, L. An indirect method for absorption rate estimation: Flurothyl-induced seizures. Bltn Mathcal Biology 59, 569–579 (1997). https://doi.org/10.1007/BF02459466
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DOI: https://doi.org/10.1007/BF02459466