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Effects of adinazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers

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Summary

Effects on psychomotor and cognitive performance of adinazolam (15 or 30 mg), alone and in combination with ethanol (0.8 g/kg), were studied in healthy male volunteers and compared to effects of 10 mg diazepam.

Adinazolam 30 mg produced relatively long-lasting impairments on tests of tracking, attention, verbal and nonverbal information processing, and memory. Adinazolam 15 mg resulted in descreased visual information processing. Adinazolam decreased supine mean arterial pressure, but only the 15 mg resulted in a tendency for decreased plasma norepinephrine concentrations.

After standing for 5 min, 30 mg adinazolam was associated with increased heart rate.

Although ethanol consumption produced additive decrements on a continuous performance task, there was little evidence to support a synergistic effect.

Adinazolam 30 mg was accompanied by increased self-reports of side effects, especially drowsiness.

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References

  1. Hollister LE (1982) Second-generation antidepressants. Ration Drug Ther 16, 12: 1–5

    Google Scholar 

  2. Amsterdam JD, Kaplan M, Potter L, Bloom L, Rickels K (1986) Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder. Psychopharm 88: 484–488

    Google Scholar 

  3. Feighner JP (1986) A review of controlled studies of adinazolam mesylate in patients with major depressive disorder. Psychopharm Bull 22: 186–191

    Google Scholar 

  4. Smith WT, Glaudin V (1986) Double-blind efficacy and safety study comparing adinazolam mesylate and placebo in depressed patients. Acta Psychiatr Scand 74: 238–245

    Google Scholar 

  5. Straw RN, Pyke RE, Von Voigtlander PF, Collins RJ, Clarke GL (1983) Clinical brochure on adinazolam (U-41, 123F, IND 12039)

  6. Papart P, Ansseau M, Cerfontaine J-L, Franck G (1986) Adinazolam-induced mania. Am J Psychiatry 143: 684–685

    Google Scholar 

  7. Linnoila M (1983) Benzodiazepines and performance. In: Costa E (ed) Benzodiazepines: from molecular biology to clinical practice. Raven, New York, pp 267–278

    Google Scholar 

  8. Milner G (1969) Drinking and driving in 753 general practice and psychiatric patients. Br J Psychiatry 115: 99–100

    Google Scholar 

  9. Reference deleted

  10. Locniskar A, Greenblatt DJ (1988) High performance liquid chromatographic assay of adinazolam and its desmethyl metabolite. J Chrom 424: 215–217

    Google Scholar 

  11. Rao SN, Dhar AK, Kutt H, Okamoto M (1982) Determination of diazepam and its pharmacologically active metabolites in blood by Bond Elut column extraction and reversed-phase high-performance liquid chromatography. J Chrom 231: 341–348

    Google Scholar 

  12. Mefford IN, Ota M, Stipetic M, Singleton W (1987) Application of a novel cation-exchange reagent, igepon T-77 (N-methyl oleoyl taurate), to microbore separations of alumina extracts of catecholamines from cerebrospinal fluid, plasma, urine and brain tissue with amperometric detection. J Chrom 420: 241–251

    Google Scholar 

  13. Spielberger CD, Gorsuch RL, Lushere RE (1968) Manual for the State Trait Anxiety Inventory. Florida State University Press, Gainesville

    Google Scholar 

  14. Derogatis LR, Lipman RS, Covi L (1973) The SCL-90: an outpatient psychiatric rating scale. Psychopharmacol Bull 9: 13–28

    Google Scholar 

  15. Linnoila M, Erwin CW, Cleveland WP, Logue P, Gentry D (1978) Effects of alcohol on psychomotor performance of men and women. J Stud Alcohol 39: 745–748

    Google Scholar 

  16. Weingartner H, Rudorfer MV, Buchsbaum MS, Linnoila M (1983) Effects of serotonin on memory impairments produced by ethanol. Science 221: 472–474

    Google Scholar 

  17. Linnoila M, Johnson J, Dubyoski T, Ross R, Buchsbaum M, Potter WZ, Weingartner H (1983) Effects of amitriptyline, desipramine and zimelidine, alone and in combination with ethanol, on information processing and memory in healthy volunteers. Acta Psychiatr Scand [Suppl] 308 68: 175–181

    Google Scholar 

  18. Linnoila M, Johnson J, Dubyoski K, Buchsbaum MS, Schneinin M, Kilts C (1984) Effects of antidepressants on skilled performance. Br J Clin Pharmacol 18: 109S-120S

    Google Scholar 

  19. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol 11: 345–359

    Google Scholar 

  20. Divoll M, Greenblatt DJ (1981) Alcohol does not enhance diazepam absorption. Pharm 22: 263–268

    Google Scholar 

  21. Ellinwood EH Jr, Heatherly DG, Nikaido AM, Bjornsson TD, Kilts C (1985) Comparative pharmacokinetics and pharmacodynamics of lorazepam, alprazolam and diazepam. Psychopharm 86: 392–399

    Google Scholar 

  22. Lister RG (1985) The amnestic action of benzodiazepines in man. Neurosci Biobeh Rev 9: 87–94

    Google Scholar 

  23. Cote P, Gueret P, Bourassa MG (1974) Systemic and coronary hemodynamic effects of diazepam in patients with normal and diseased coronary arteries. Circulation 50: 1210–1216

    Google Scholar 

  24. Marty J, Gauzit R, Lefevre P, Coudere E, Farinotti R, Henzel C, Desmonts JM (1986) Effects of diazepam and midazolam on baroreflex control of heart rate and on sympathetic activity in humans. Anesth Analg 65: 113–119

    Google Scholar 

  25. Roy-Byrne PP, Lewis N, Villacres E, Greenblatt DJ, Shader RI, Veith RC (1988) Suppression of norepinephrine appearance rate in plasma by diazepam in humans. Life Sci 43: 1615–1623

    Google Scholar 

  26. Logue PE, Gentry WD, Linnoila M, Erwin CW (1978) Effect of alcohol consumption on state anxiety changes in male and female alcoholics. Am J Psychiatr 135: 1079–1081

    Google Scholar 

  27. Lister RG, File SE (1983) Performance impairment and increased anxiety resulting from the combination of alcohol and lorazepam. J Clin Psychopharmacol 3: 66–71

    Google Scholar 

  28. Laisi U, Linnoila M, Seppala T, Himberg JJ, Mattila MJ (1979) Pharmacokinetic and pharmacodynamic interactions of diazepam with different alcoholic beverages. Eur J Clin Pharmacol 16: 263–270

    Google Scholar 

  29. Chan AWK (1984) Effects of combined alcohol and benzodiazepine: A review. Drug Alcohol Depend 13: 315–341

    Google Scholar 

  30. Hoyumpa AM (1984) Alcohol interactions with benzodiazepines and cocaine. Adv Alcohol Subst Abuse 3: 21–24

    Google Scholar 

  31. Sellers EM, Busto U (1982) Benzodiazepines and ethanol: Assessment of the effects and consequences of psychotropic drug interactions. J Clin Psychopharmacol 2: 249–262

    Google Scholar 

  32. Scavone JM, Greenblatt DJ, Harmatz JS, Shader RI (1986) Kinetic and dynamic interaction of brotizolam and ethanol. Br J Clin Pharmacol 21: 197–204

    Google Scholar 

  33. Ochs HR, Greenblatt DJ, Arendt RM, Hubbel W, Shader RI (1984) Pharmacokinetic noninteraction of triazolam and ethanol. J Clin Psychopharmacol 4: 106–107

    Google Scholar 

  34. Ticku MK, Burch TP, Davis WC (1983) The interactions of ethanol with the benzodiazepine-GABA receptor-ionophore complex. Pharmacol Biochem Behav 18: 15–18

    Google Scholar 

  35. Palva ES, Linnoila M, Saario I, Mattila MJ (1979) Acute and subacute effects of diazepam on psychomotor skills: Interactions with alcohol. Acta Pharmacol Toxicol 49: 257–264

    Google Scholar 

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Linnoila, M., Stapleon, J.M., Lister, R. et al. Effects of adinazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers. Eur J Clin Pharmacol 38, 371–377 (1990). https://doi.org/10.1007/BF00315578

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  • DOI: https://doi.org/10.1007/BF00315578

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