Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Tofisopam, a novel 3,4,-benzodiazepine: Multiple-dose effects on psychomotor skills and memory. Comparison with diazepam and interactions with ethanol


Twelve healthy male volunteers were treated (double-blind crossover design) with tofisopam (a new 3,4-benzodiazepine), diazepam, or placebo, on 2 consecutive days each. Psychomotor skills were impaired after a single dose of diazepam (10 mg) given on day 1. Measurements on day 2 showed that some tolerance had developed to the diazepam-induced impairment of reactive and coordinative skills, but not to its effects on flicker fusion or on the extraocular muscle balance. Tofisopam failed to impair performance both as a single dose (100 mg) and after repeated doses (100+50+50+100 mg). The subjects felt more fatigue, dizziness, calmness, and passiveness after diazepam than after tofisopam. When either drug was given together with 0.8 g/kg ethanol on day 2, the breath ethanol concentrations were 0.7–1.0 mg/ml and all psychomotor skills were impaired. Diazepam+ethanol particularly impaired memory and learning as well. After this combination the subjects were classified (time anticipation test) as ‘disqualified drivers’ more often than after placebo. It is concluded that diazepam,as well as either benzodiazepine with ethanol, may reduce the ability to drive vehicles or operate machinery.

This is a preview of subscription content, log in to check access.


  1. Bliding, Å.: Effects of different rates of absorption of two benzodiazepines on subjective and objective parameters. Eur. J. Clin. Pharmacol. 7, 201–211 (1974)

  2. Gerevich, J., Bolla, K., Tóth, K., Sebo, J.: The effect of grandaxin on lorry drivers. Ther. Hung. 23, 143–146 (1975)

  3. Hannington-Kiff, J. G.: Measurements of recovery from outpatient general anaesthesia with a simple ocular test. Br. Med. J. 3, 132–135 (1970)

  4. Hilgard, E. R.: Methods and procedures in the study of learning. In: Handbook of experimental psychology, S. S. Steven, ed., pp. 517–567. New York: Wiley 1951

  5. Hindmarch, I.: A 1,4-benzodiazepine, temazepam (K-3917), its effects on some psychological parameters of sleep and behaviour. Arzneim, Forsch. 25, 1836–1839 (1975)

  6. Juhasz, P.: EGYT Documentation. EGYT pharmacochemical works: Budapest 1976

  7. Korosi, J., Lang, T.: Investigations with 5H-2,3-henzodiazepines. Ther. Hung. 23, 132–133 (1975)

  8. Laisi, U., Linnoila, M., Seppälä, T., Mattila, M. J., Himberg, J. J.: Pharmacokinetic and pharmacodynamic interaction of diazepam and different alcoholic beverages. Eur. J. Clin. Pharmacol. 16, 263–270 (1979)

  9. Liljequist, R., Mattila, M. J.: Acute effects of temazepam and nitrazepam on psychomotor skills and memory. Acta Pharmacol. Toxicol. (Kbh.) 44, 364–369 (1979)

  10. Liljequist, R., Seppälä, T., Mattila, M. J.: Amitriptyline-and mianserine-induced changes in acquisition of paired-association learning task. Br.J. Clin. Pharmacol. 5, 149–153 (1978)

  11. Linnoila, M.: Drug effects on psychomotor skills related to driying: Interaction of atropine, glycopyrrhonium and alcohol.Eur. J. Clin. Pharmacol. 6, 107–112 (1973)

  12. Linnoila, M., Mattila, M. J.: Drug interaction on psychomotor skills related to driving: Diazepam and alcohol. Eur. J. Clin. Pharmacol. 5, 186–194 (1973)

  13. MacLeod, S. M., Giles, H. G., Patzalek, G., Thiessen, J. J., Sellers, E. M.: Diazepam actions and plasma concentrations following ethanol ingestion. Eur. J. Clin. Pharmacol. 11, 345–349 (1977)

  14. Maruyama, K., Kitamura, S.: Speed anticipation test: A test for discrimination of accident proneness in motor driver. Tohoku Psychol. Folia 20, 13–20 (1961)

  15. Mattila, M. J., Palva, E., Seppälä, T., Ostrovskaya, R. U.: Actions and interactions with alcohol of drugs on psychomotor skills: Comparison of diazepam and γ-hydroxybutyric acid. Arch. Int. Pharmacodyn. Ther. 234, 236–246 (1978)

  16. Orr, J., Dussault, P., Chappel, C., Goldberg, L., Reggiani, G.: Relation between drug-induced central nervous system effects and plasma levels of diazepam in man. Mod. Probl. Pharmacopsychiatry 11, 57–67 (1976)

  17. Palva, E. S., Linnoila, M.: Effect of active metabolites of chlordiazepoxide and diazepam, alone or in combination with alcohol, on psychomotor skills related to driving. Eur. J. Clin. Pharmacol. 13, 345–350 (1978)

  18. Petrocz, L., Kosóczky, I.: The main pharmacological characteristics of grandaxin (tofisopam. EGYT-341). Ther. Hung. 23, 134–138 (1975)

  19. Rónai, S., Orosz, F., Bolla, K.: Human pharmacokinetic data on grandaxin. Ther. Hung. 23, 139–142 (1975)

  20. Seppälä, T., Linnoila, M., Mattila, M. J.: Drugs, alcohol and driving. Drugs 17, 389–408 (1979)

  21. Simonson, E., Brozek, J.: Flicker fusion frequency. Background and applications. Physiol. Rev. 32, 349–378 (1952)

  22. Szobor, A.: Treatment of psychic disorders accompanying myasthenia gravis (grandaxin, a new non-relaxant tranquilizer). Ther. Hung. 23, 159–163 (1975)

  23. Várady, G., Bolla, K., Sebo, J.: The clinical evaluation of grandaxin used in the treatment of outpatients (a multicentric study). Ther. Hung. 23, 153–158 (1975)

Download references

Author information

Correspondence to T. Seppälä.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Seppälä, T., Palva, E., Mattila, M.J. et al. Tofisopam, a novel 3,4,-benzodiazepine: Multiple-dose effects on psychomotor skills and memory. Comparison with diazepam and interactions with ethanol. Psychopharmacology 69, 209–218 (1980). https://doi.org/10.1007/BF00427652

Download citation

Key words

  • Tofisopam
  • Diazepam
  • Ethanol
  • Interaction
  • Tolerance
  • Psychomotor skills