, Volume 51, Issue 1, pp 59–64 | Cite as

The relationship between the anticonvulsant properties of SC-13504 and its plasma levels, measured by polarography, in baboons with photosensitive epilepsy

  • B. S. Meldrum
  • M. R. Smyth
  • W. Franklin-Smyth
  • J. M. Clifford
Animal Studies


SC-13504 was given intravenously to baboons with photosensitive epilepsy, Papio papio, with and without prior administration of allylglycine. Plasma levels of the drug were determined by differential pulse polarography and correlated with behavioural changes and the anticonvulsant action of the drug. Protection against photically induced seizures or self-sustaining myoclonic responses was seen 30 to 120 min after SC-13504, 4–8 mg/kg (when plasma levels were 1 μg/ml or greater). EEG and neurological signs of toxicity were seen after SC-13504 8 mg/kg but not after 4–6 mg/kg.

Key words

Anticonvulsant SC-13504 Photosensitive baboons Plasma level Polarography 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Craig, C. R.: Anticonvulsant properties of some benzhydrylpiperazine and benzhydrylpiperidine compounds. Arch. int. Pharmacodyn 165, 328–336 (1967)Google Scholar
  2. Edmonds, H. L., Stark, L. G., Rinne, S.: The effect of SC-13504 on electrically induced hippocampal stimulation in chronic cats. Proc. West. Pharmacol. Soc. 17, 77–81 (1974)Google Scholar
  3. Gilbert, J. C., Wyllie, M.: Effects of anticonvulsant drugs and convulsant drugs on the ATPase activities of synaptosomes and their components. Brit. J. Pharmacol. 56, 49–57 (1976)Google Scholar
  4. Horton, R. W., Meldrum, B. S.: Seizures induced by allylglycine, 3-mercaptoproprionic acid and 4-deoxypyridoxine in mice and photosensitive baboons and different modes of inhibition of cerebral glutamic acid decarboxylase. Brit. J. Pharmacol. 49, 52–63 (1973)Google Scholar
  5. Joy, R. M., Edmonds, H. L.: The antagonism of hippocampal and cortical afterdischarge by SC-13504, a new anticonvulsant. Neuropharmacology 13, 145–157 (1974)Google Scholar
  6. Killam, E. K.: The anticonvulsant activity of a new compound (SC-13504) in Papio papio. Proc. West. Pharmacol. Soc. 17, 33–36 (1974)Google Scholar
  7. Killam, K. F., Killam, E. K., Naquet, R.: An animal model of light sensitive epilepsy. Electroenceph. clin. Neurophysiol. 22, 497–513 (1967)Google Scholar
  8. Meldrum, B. S., Anlezark, G., Balzamo, E., Horton, R. W., Trimble, M.: Photically induced epilepsy in Papio papio as a model for drug studies. Adv. Neurol., Vol. 10, B. S. Meldrum and C. D. Marsden, eds., pp. 119–128. New York: Raven Press 1975aGoogle Scholar
  9. Meldrum, B. S., Balzamo, E., Gadea, M., Naquet, R.: Photic and drug-induced epilepsy in the baboon (Papio papio). The effects of isoniazid, thiosemicarbazide, pyridoxine and amino-oxyacetic acid. Electroenceph. clin. Neurophysiol. 29, 333–347 (1970)Google Scholar
  10. Meldrum, B. S., Horton, R. W.: Convulsive effects of 4-deoxypyridoxine and of bicuculline in photosensitive baboons (Papio papio) and rhesus monkeys (Macaca mulatta). Brain Res. 35, 414–436 (1971)Google Scholar
  11. Meldrum, B. S., Horton, R. W., Toseland, P. A.: A primate model for testing anticonvulsant drugs. Arch. Neurol. (Chic.) 32, 289–294 (1975b)Google Scholar
  12. Smyth, M. R., Franklin-Smyth, W., Palmer, R. F., Clifford, J. M.: A polarographic and U-V spectral investigation of SC-13504, a pharmacologically active benzhydryl-piperazine derivative. Analyst 101, 469–477 (1976)Google Scholar
  13. Stark, L. G., Killam, K. F., Killam, E. K.: The anticonvulsant effects of phenobarbital, diphenylhydantoin and two benzodiazepines in the baboon. Papio papio. J. Pharmacol. exp. Ther. 173, 125–132 (1970)Google Scholar
  14. Stark, L. G., Edmonds, H. L.: The anticonvulsant effects of SC-13504 in an animal model of epilepsy. Proc. West. Pharmacol. Soc. 16, 123–125 (1973)Google Scholar

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • B. S. Meldrum
    • 1
  • M. R. Smyth
    • 2
  • W. Franklin-Smyth
    • 2
  • J. M. Clifford
    • 3
  1. 1.Department of NeurologyInstitute of PsychiatryLondon
  2. 2.Department of ChemistryChelsea CollegeLondon
  3. 3.Scientific Affairs DivisionG. D. Searle and Company Ltd.High WycombeEngland

Personalised recommendations