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. 1985 Nov;20(5):492–496. doi: 10.1111/j.1365-2125.1985.tb05105.x

Tofisopam and midazolam: differences in clinical effects and in changes of CSF monoamine metabolites.

M Hovi-Viander, J Kanto, H Scheinin, M Scheinin
PMCID: PMC1400718  PMID: 2416331

Abstract

The effect of two repeated oral doses of 100 mg tofisopam 15 mg midazolam and placebo on the concentrations of monoamine metabolites (MHPG, 5-HIAA, HVA) in lumbar CSF were studied in general surgical patients operated on under spinal analgesia (n = 12 in each group). Midazolam, but not tofisopam, improved the quality of sleep the night before surgery. Both active agents reduced preoperative anxiety of the patients, but tofisopam was without subjective sedative action. In the placebo group, in contrast to the active drug groups, there was a slight positive correlation between the MHPG concentration and degree of anxiety before surgery. The only significant difference in the monoamine metabolites in lumbar CSF was found in the concentrations of HVA between tofisopam and placebo treated patients. The lower HVA concentrations suggest that the curious 3,4-benzodiazepine derivative, tofisopam, modifies central dopaminergic activity.

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Selected References

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  1. Charney D. S., Heninger G. R., Redmond D. E., Jr Yohimbine induced anxiety and increased noradrenergic function in humans: effects of diazepam and clonidine. Life Sci. 1983 Jul 4;33(1):19–29. doi: 10.1016/0024-3205(83)90707-5. [DOI] [PubMed] [Google Scholar]
  2. Costa E., Guidotti A. Molecular mechanisms in the receptor action of benzodiazepines. Annu Rev Pharmacol Toxicol. 1979;19:531–545. doi: 10.1146/annurev.pa.19.040179.002531. [DOI] [PubMed] [Google Scholar]
  3. DUNDEE J. W., MOORE J., NICHOLL R. M. Studies of drugs given before anaesthesia. I. A method of pre-operative assessment. Br J Anaesth. 1962 Jul;34:458–463. doi: 10.1093/bja/34.7.458. [DOI] [PubMed] [Google Scholar]
  4. Goldberg H. L., Finnerty R. J. Comparative efficacy of tofisopam and placebo. Am J Psychiatry. 1979 Feb;136(2):196–199. doi: 10.1176/ajp.136.2.196. [DOI] [PubMed] [Google Scholar]
  5. Kanto J. Benzodiazepines as oral premedicants. Br J Anaesth. 1981 Nov;53(11):1179–1188. doi: 10.1093/bja/53.11.1179. [DOI] [PubMed] [Google Scholar]
  6. Kanto J., Kangas L., Leppänen T., Mansikka M., Sibakov M. L. Tofizopam: a benzodiazepine derivative without sedative effect. Int J Clin Pharmacol Ther Toxicol. 1982 Jul;20(7):309–312. [PubMed] [Google Scholar]
  7. Nordin C., Siwers B., Bertilsson L. Bromocriptine treatment of depressive disorders. Clinical and biochemical effects. Acta Psychiatr Scand. 1981 Jul;64(1):25–33. doi: 10.1111/j.1600-0447.1981.tb00758.x. [DOI] [PubMed] [Google Scholar]
  8. Nordin C., Siwers B., Bertilsson L. Site of lumbar puncture influences levels of monoamine metabolites. Arch Gen Psychiatry. 1982 Dec;39(12):1445–1445. doi: 10.1001/archpsyc.1982.04290120075017. [DOI] [PubMed] [Google Scholar]
  9. Pakkanen A., Kanto J., Kangas L., Mansikka M. Comparative study of the clinical effects of tofizopam, nitrazepam and placebo as oral premedication. Br J Anaesth. 1980 Oct;52(10):1009–1012. doi: 10.1093/bja/52.10.1009. [DOI] [PubMed] [Google Scholar]
  10. Petöcz L., Kosóczky I. The main pharmacological characteristics of Grandaxin (tofizopam, EGYT-341). Ther Hung. 1975;23(4):134–138. [PubMed] [Google Scholar]
  11. Pieri L., Schaffner R., Scherschlicht R., Polc P., Sepinwall J., Davidson A., Möhler H., Cumin R., Da Prada M., Burkard W. P. Pharmacology of midazolam. Arzneimittelforschung. 1981;31(12A):2180–2201. [PubMed] [Google Scholar]
  12. Saano V., Urtti A., Airaksinen M. M. Increase in 3H-flunitrazepam binding in vitro and in vivo to rat brain benzodiazepine receptors by tofizopam, a 3,4-benzo-diazepine. Pharmacol Res Commun. 1981 Jan;13(1):75–85. doi: 10.1016/s0031-6989(81)80040-9. [DOI] [PubMed] [Google Scholar]
  13. Scheinin M., Chang W. H., Kirk K. L., Linnoila M. Simultaneous determination of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid in cerebrospinal fluid with high-performance liquid chromatography using electrochemical detection. Anal Biochem. 1983 May;131(1):246–253. doi: 10.1016/0003-2697(83)90162-8. [DOI] [PubMed] [Google Scholar]
  14. Seppälä T., Palva E., Mattila M. J., Korttila K., Shrotriya R. C. Tofisopam, a novel 3,4-benzodiazepine: multiple-dose effects on psychomotor skills and memory. Comparison with diazepam and interactions with ethanol. Psychopharmacology (Berl) 1980;69(2):209–218. doi: 10.1007/BF00427652. [DOI] [PubMed] [Google Scholar]
  15. Sjovall S., Kanto J., Grönroos M., Himberg J. J., Kangas L., Viinamäki O. Antidiuretic hormone concentrations following midazolam premedication. Anaesthesia. 1983 Dec;38(12):1217–1220. doi: 10.1111/j.1365-2044.1983.tb12529.x. [DOI] [PubMed] [Google Scholar]
  16. Sjövall S., Kanto J., Iisalo E., Himberg J. J., Kangas L. Midazolam versus atropine plus pethidine as premedication in children. Anaesthesia. 1984 Mar;39(3):224–228. doi: 10.1111/j.1365-2044.1984.tb07231.x. [DOI] [PubMed] [Google Scholar]
  17. Sjövall S., Kanto J., Iisalo E., Kangas L., Mansikka M., Pihlajamäki K. Use of atropine in connection with oral midazolam premedication. Int J Clin Pharmacol Ther Toxicol. 1984 Apr;22(4):184–188. [PubMed] [Google Scholar]
  18. Sjövall S., Kanto J., Kangas L., Pakkanen A. Comparison of midazolam and flunitrazepam for night sedation. A randomised double-blind study. Anaesthesia. 1982 Sep;37(9):924–928. doi: 10.1111/j.1365-2044.1982.tb01854.x. [DOI] [PubMed] [Google Scholar]
  19. Várady G., Bolla K., Sebö J. The clinical evaluation of Grandaxin used in the treatment of outpatients (a multicentric study). Ther Hung. 1975;23(4):153–158. [PubMed] [Google Scholar]

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