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Chromosome Studies on the Effect of Primidon (MylepsinumR) and Its Metabolites, Phenobarbital and Phenylethylmalondiamide, in Vitro

Published online by Cambridge University Press:  01 August 2014

Dieter Foerst
Dieter Foerst*
Affiliation:
Institut für Humangenetik und Anthropologie der Universität Erlangen-Nürnberg
*
Institut für Humangenetik und Anthropologie der Universität, Bismarckstrasse 10, 8520 Erlangen, German Federal Republic

Summary

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Primidone and its metabolites Phenobarbital and Phenylethylmalondiamide were tested in cultures of human lymphocytes on possible effects of inducing chromosome aberrations. The substances examined ranged from concentrations lower than the therapeutic serum level to 10-75 times this value, which differed with the various substances. Phenylethylmalondiamide shows, besides an increase of spiralization defects at higher concentrations, which was typical for all three substances, no reaction on the chromosome structure.

By using the Friedman-test a statistically significant difference (P < 5%) could be found between the average aberration rates of the controls and the cultures which had been treated with Primidone and Phenobarbital. The test according to Wilcoxon and Wilcox shows that there is a statistically significant (P < 5%) difference between the aberration rates of controls and the respectively treated cultures. The higher values for percentage of aberrant mitoses are caused by the increase of gaps and breaks. There was, however, no proof for a linear dependence of the percentage of aberrant mitoses on the increasing concentrations of the substances. The number of tetraploid mitoses, endoreduplications and hyperploid cells was within the normal range.

Since in these investigations the number of chromosome exchanges was not increased, it can certainly be said that Primidone and Phenobarbital are not highly mutagenic substances.

Type
Research Article
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 21 , Issue 4 , October 1972 , pp. 305 - 318
Copyright
Copyright © The International Society for Twin Studies 1978

References

LITERATUR

Aladj, H. 1961. Experimentelle Auslösung chromosomaler Verteilungsstörungen in menschlichen Leukozyten durch in vitro-Zusatz verschiedener Narkotika. — Diss., Düsseldorf.Google Scholar
Ayraud, N., Kermarec, J., Martinon, J. 1968. Effets cytogénétiques des médicaments anticonvulsivants. Ann. Genet., 11: 253–257.Google Scholar
Bogue, J.Y., Carrington, H.C. 1952. Personal communication. In: L.S. Goodman et al. 1953.Google Scholar
Bogue, J.Y., Carrington, H.C. 1953. The evaluation of “mysoline” — A new anticonvulsant drug. Br. J. Pharmacol., 8: 230–236.Google ScholarPubMed
Booker, H.E., Hosokowa, K., Burdette, R.D., Darcey, B. 1970. A clinical study of serum primidone levels. Epilepsia, 11: 395–402.CrossRefGoogle ScholarPubMed
Butler, T.C., Waddell, W.J. 1956. Metabolic conversion of primidone (mysoline) to phenobarbital. Proc. Soc. Exp. Biol. Med., 93: 544–546.Google Scholar
Caratzali, A., Roman, J.-C., Turpin, R. 1969. Action stathmocinétique de quelques dérivés barbituriques sur le lymphocyte humain en culture. C. R. Acad. Se. (Paris), 268: 191–192.Google Scholar
Fujimoto, J.M., Mason, W.H., Murphy, M. 1968. Urinary excretion of primidone and its metabolites in rabbits. J. Pharmacol., 159: 379–388.Google Scholar
Gebhart, E. 1970 a. Beiträge zur chemíschen Mutagenese beim Menschen. Sitzungsberichte der physikal.-med. Sozietät zu Erlangen 83/84 (1970) 18–31.Google Scholar
Gebhart, E. 1970 b. The treatment of human chromosomes in vitro: results. In Vogel, F. and Röhrborn, G. (Hrsg): Chemical Mutagenesis in Mammals and Man. Springer-Verlag, Berlin-Heidelberg-New York.Google Scholar
German, J., Ehlers, K.H., Kowal, A., De George, F.V., Engle, A., Passarge, E. 1970. Possible teratogeneticity of trimethadione and paramethadione. Lancet 2: 261–167.CrossRefGoogle Scholar
Gleiss, J. 1968. Überlegung zur Teratogenität von Schlafmitteln. Dtsch. Med. Wochenschr., 93: 1732–1734.Google Scholar
Goodman, L.S., Swinyard, E.A., Brown, W.C., Schiffman, D.O., Grewal, M.S., Bliss, E.L. 1953. Anticonvulsant properties of 5-phenyl-5-ethyl-hexa-hydro-pyrimidine-4,6-dione (mysoline), a new antiep-ileptic. J. Pharmacol., 108: 428–436.Google Scholar
Große, K.-P., Schwanitz, G., Rott, H.-D., Wißmüller, H.F. 1972. Chromosomenuntersuchungen bei Behandlung mit Antikonvulsiva. Humangenetik, 16: 209–216.Google Scholar
Grote, W., Kabarity, A., Schade, H. 1970. Auswirkungen eines Barbitursäurederivates auf die Embryogenese von Kaninchen durch Mitosestörungen. Humangenetik, 8: 280–288.Google Scholar
Livingston, S. 1966. Drug Therapy for Epilepsy. Charles C. Thomas, Springfield, pp. 234.Google Scholar
Mark, L.C. 1963. Metabolism of barbiturates in man. Clin. Pharmacol. Ther., 4: 504–530.Google Scholar
Meadow, S.R. 1968. Anticonvulsant drugs and congenital abnormalities. Lancet 2: 1296.Google Scholar
Moorhead, P.S., Nowell, P.S., Mellman, W.J., Battips, D.M., Hungerford, D.A. 1960. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp. Cell. Res., 20: 613–616.Google Scholar
Pashayan, H., Pruzansky, D., Pruzansky, S. 1971. Are anticonvulsants teratogenic? Lancet 2: 702–703.Google Scholar
Neuhäuser, G., Schwanitz, G., Rott, H.D. 1970. Zur Frage mutagener und teratogener Wirkung von Antikonvulsiva. Fortschr. Med., 19: 819–820.Google Scholar
Olesen, O.V., Dam, M. 1967. The metabolic conversion of primidone (MysolineR) to phenobarbitone in patients under long-term treatment. Acta Neurol. Scand., 43: 348–356.Google Scholar
Persaud, T.V.N., Henderson, W.M. 1969. The teratogenicity of barbital sodium in mice. Arzneim. Forsch., 8: 1309–1310.Google Scholar
Pippenger, C.E., Gillen, H.W. 1969. Gas chromatographic analysis for anticonvulsant drugs in biological fluids. Clin. Chem., 15: 582–590.CrossRefGoogle Scholar
Plaa, G.L., Fujimoto, J.M., Hine, C.H. 1958. Intoxication from primidone due to its biotransformation to phenobarbital. J. Am. Med. Ass., 168: 1769–1770.Google Scholar
Röhrborn, G. 1970. The dominant lethals: method and cytogenetic examination of early cleavage stages. In: Vogel, F. and Röhrborn, G. (Hrsg.): Chemical Mutagenesis in Mammals and Man. Springer-Verlag, Berlin-Heidelberg-New York.Google Scholar
Sachs, L. 1968. Statistische Auswertungsmethoden. Springer-Verlag, Berlin-Heidelberg-New York.CrossRefGoogle Scholar
Saxl, O. 1972. Nebenwirkungen von Barbituraten. Fortschr. Med., 2: 50–54.Google Scholar
Swinyard, E.A., Tedeschi, D.H., Goodman, L.S. 1954. Effects of liver damage and nephrectomy on anticonvulsant activity of mysoline and phenobarbital. J. Am. Pharm. Assoc., 43: 114–116.Google Scholar