Central effects in man of the novel schistosomicidal benzodiazepine meclonazepam (original) (raw)

Summary

The novel benzodiazepine derivative, meclonazepam (3-methylclonazepam) has been found to be orally effective at high doses against all stages of schistosomiasis. Animals studies have shown it to have a high therapeutic index and a profile of behavioural activity typical of the benzodiazepines. The effects of single oral doses of meclonazepam, 1, 2 and 4 mg on central arousal, psychomotor performance and subjective mood were studied in two double-blind placebo controlled studies in healthy volunteers. In doses exceeding 1 mg, meclonazepam caused marked dose-related impairment in cognitive and psychomotor functions as well as shifts in mood reflecting sedation and ataxia. These effects were most prominent in the first 3 h after administration, with moderate sedation still present 6 h after the 4 mg dose. The implications of these findings for the use of benzodiazepine agents in the treatment of schistosomiasis are discussed.

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References

  1. Baard AP, Sommers DK, Honiball PJ, Fourie ED, du Toit LE (1979) Preliminary results in human schistosomiasis with Ro 11-3128. S Afr Med J 55: 617–618
    Google Scholar
  2. Bennett JL (1980) Characteristics of antischistosomal benzodiazepine binding sites in Schistosoma mansoni. J Parasitol 66: 742–747
    Google Scholar
  3. Bond AJ, Lader MH (1973) The residual effects of flurazepam. Psychopharmacologia (Berl) 32: 223–255
    Google Scholar
  4. Bond AJ, Lader MH (1974) The use of visual analogue scales in rating subjective feelings. Br J Med Psychol 47: 211–218
    Google Scholar
  5. Clarke PRF, Eccersley PS, Frisby JP, Thornton JA (1970) The amnesic effect of valium. Br J Anaesth 42: 690–697
    Google Scholar
  6. Darragh A, Lambe R, Kenny M, Brick I, Taaffe W, O'Boyle C (1982a) Ro 15-1788 antagonises the central effects of diazepam in man without altering diazepam bioavailability. Br J Clin Pharmacol 14: 677–682
    Google Scholar
  7. Darragh A, Lambe R, Brick I, O'Boyle C (1982b) Antagonism of the central effects of 3-methylclonazepam. Br J Clin Pharmacol 14: 871–872
    Google Scholar
  8. Eysenck JJ, Eysenck SBG (1964) Manual for the Eysenck personality inventory. University of London Press
  9. Ghoneim MM, Mewaldt SP (1975) Effects of diazepam and scopolamine on storage, retrieval and organisational processes in memory. Psychopharmacologia (Berl) 44: 257–262
    Google Scholar
  10. Hunkeler W, Mohler H, Pieri L, Polc R, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290: 514–516
    Google Scholar
  11. Kanto J (1981) Benzodiazepines as oral premedicants. Br J Anaesth 53: 1179–1188
    Google Scholar
  12. McKay AC, Dundee JW (1980) Effect of oral benzodiazepines on memory. Br J Anaesth 52: 1247–1257
    Google Scholar
  13. McNair DM (1973) Anti-anxiety drugs and human performance. Arch Gen Psychiatr 29: 611–617
    Google Scholar
  14. Mohler H, Okada J (1977) Benzodiazepine receptor demonstration in the central nervous system. Science 198: 849–851
    Google Scholar
  15. O'Boyle CA, Harris D (1984) Sedative and anxiolytic effects of oral temazepam. Ir J Med Sci 153: 39–40
    Google Scholar
  16. O'Boyle CA, Lambe R, Darragh A, Brick I (1983a) Antagonism of the central effects of meclonazepam in man by Ro 15-1788. Ir J Med Sci 152: 210–211
    Google Scholar
  17. O'Boyle CA, Lambe R, Darragh A, Taaffe W, Brick I, Kenny M (1983b) Ro 15-1788 antagonises the effects of diazepam in man without affecting its bioavailability. Br J Anaesth 55: 349–355
    Google Scholar
  18. O'Boyle CA, Lambe R, Darragh A, Brick I (1984) The central effects of acute and repeated doses of meclonazepam in man. Br J Clin Pharmacol 17: 202P.
  19. Pax R, Bennett JL, Fetterer R (1978) A benzodiazepine derivative and praziquantel: Effects on musculature of Schistosoma mansoni and Schistosoma japonicum. Naunyn Schmiedeberg's Arch Pharmacol 304: 309–315
    Google Scholar
  20. Schallek W (1978) Pre-clinical pharmacology of the anxiolytics. In: Clarke WG, DelGiudice J (eds) Principles of psychopharmacology. Academic Press, New York, pp 325–342
    Google Scholar
  21. Stohler HR (1978) Ro 11-3128, a novel schistosomicidal compound. In: Siegenthaler W, Luthy R (eds) Current chemotherapy. Proceedings of the 10th International Congress of Chemotherapy, vol 1. American Society for Microbiology, Washington DC, pp 147–148
    Google Scholar
  22. Wittenborn JR (1978) Behavioural toxicity in normal humans as a model for assessing behavioural toxicity in patients. In: Lipton JA, Di Mascio A, Killam KF (eds) Psychopharmacology: A generation of progress. Raven Press, New York, pp 791–797
    Google Scholar
  23. Wittenborn JR (1979) Effects of benzodiazepines on psychomotor performance. Br J Clin Pharmacol 7 [Suppl 1]: 61s-67s
    Google Scholar

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Authors and Affiliations

  1. Psychosomatic Unit, Department of Psychiatry, University College Dublin, St. James's Hospital, Dublin, Ireland
    C. O'Boyle
  2. Institute of Clinical Pharmacology, Dublin, Ireland
    R. Lambe & A. Darragh

Authors

  1. C. O'Boyle
  2. R. Lambe
  3. A. Darragh

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O'Boyle, C., Lambe, R. & Darragh, A. Central effects in man of the novel schistosomicidal benzodiazepine meclonazepam.Eur J Clin Pharmacol 29, 105–108 (1985). https://doi.org/10.1007/BF00547377

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