Abstract
In a placebo controlled, crossover study psychomotor effects of single doses of diazepam, 10 and 20 mg, flunitrazepam, 1 and 2 mg, as well as 0.9 g ethanol/kg body weight were investigated over a time period of 6 h in 12 healthy men. Blood samples were collected simultaneously with the test sessions to determine drug concentrations in plasma or blood. The ethanol dose caused the least performance impairment, followed by 10 mg diazepam. The most pronounced impairment was caused by 2 mg flunitrazepam, whereas 20 mg diazepam and 1 mg flunitrazepam caused intermediate impairment and were approximately equipotent on group level. Considerable interindividual differences with respect to maximal impairment following a particular drug treatment were observed, with poor correlation between individual maximal impairments and individual peak plasma concentrations of the drug. The maximal impairment in simple reaction time following the flunitrazepam treatments occurred earlier relative to the peak plasma concentration of the drug as compared to the diazepam treatments. This may indicate that acute tolerance develops differently for the two drugs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arendt RM, Greenblatt DJ, deJong RH, Bonin JD, Abernethy DR, Ehrenberg BL, Giles HG, Sellers EM, Shader RI (1983) In vitro correlates of benzodiazepine cerebrospinal fluid uptake, pharmacodynamic action and peripheral distribution. J Pharmacol Exp Ther 227:98–106
Bond AJ, Hailey DM, Lader MH (1977) Plasma concentrations of benzodiazepines. Br J Clin Pharmacol 4:51–56
Bonnichsen RK, Theorell H (1951) An enzymatic method for microdetermination of ethanol. Scand J Clin Lab Invest [suppl] 3:58–62
Colburn WA, Jack ML (1987) Relationships between CSF concentrations, receptor binding characteristics, and pharmacokinetic and pharmacodynamic properties of selected 1,4-substituted benzodiazepines. Clin Pharmacokinet 13:179–181
Ellinwood EH, Linnoila M, Easler ME, Molter DW (1983) Profile of acute tolerance to three sedative anxiolytics. Psychopharmacology 79:137–141
Ellinwood EH, Nikaido AM, Heatherly DG, Bjornsson TD (1987) Benzodiazepine pharmacodynamics: evidence for biophase rate limiting mechanisms. Psychopharmacology 91:168–174
Erwin CW, Linnoila M, Hartwell J, Erwin A, Guthrie S (1986) Effects of buspirone and diazepam, alone and in combination with alcohol, on skilled performance and evoked potentials. J Clin Psychopharmacol 6:199–209
Ghoneim MM, Mewaldt SP, Hinrichs JV (1984) Dose-response analysis of the behavioral effects of diazepam: II. Psychomotor performance, cognition and mood. Psychopharmacology 82:296–300
Greenblatt DJ, Ochs HR, Lloyd BL (1980) Entry of diazepam and its major metabolite into cerebrospinal fluid. Psychopharmacology 70:89–93
Haffner JFV, Mørland J, Setekleiv J, Strømsæther CE, Danielsen A, Frivik PT, Dybing F (1973) Mental and psychomotor effects of diazepam and ethanol. Acta Pharmacol Toxicol 32:161–178
Higgins ST, Bickel WK, O'Leary DK, Yingling J (1987) Acute effects of ethanol and diazepam on the acquisition and performance of response sequences in humans. J Pharmacol Exp Ther 243:1–8
Jansen AAI, Verbaten MN, Slangen JL (1988) Acute effects of bromazepam on signal detection performance, digit symbol substitution test and smooth pursuit eye movements. Neuropsychobiology 20:91–95
Kleinknecht RA, Donaldson D (1975) A review of the effects of diazepam on cognitive and psychomotor performance. J Nerv Ment Dis 161:399–414
Mandema JW, Sansom LN, Dios-Vièitez MC, Hollander-Jansen M, Danhof M (1991) Pharmacokinetic-pharmacodynamic modelling of the electroencephalographic effects of benzodiazepines. Correlation with receptor binding and anticonvulsant activity. J Pharmacol Exp Ther 257:472–478
Massotti M, Schlichting JL, Antonacci MD, Giusti P, Memo M, Costa E, Guidotti A (1991) γ-Aminobutyric acidA receptor heterogeneity in rat central nervous system: studies with clonazepam and other benzodiazepine ligands. J Pharmacol Exp Ther 256:1154–1160
Meyer T (1978) Determination of alcohol in biological samples by headspace gas chromatography using a glass capillary column. Acta Pharmacol Toxicol 43:164–168
Palva ES, Linnoila M (1978) 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
Pritchett DP, Seeburg PH (1990) γ-Aminobutyric acidA receptor α5-subunit creates novel type II benzodiazepine receptor pharmacology. J Neurochem 54:1802–1804
Pritchett DP, Lüddens H, Seeburg PH (1989) Type I and type II GABAA-benzodiazepine receptors produced in transfected cells. Science 245:1389–1392
Schofield PR, Darlison MG, Fujita N, Burt DC, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA, Seeburg PH, Barnard EA (1987) Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family. Nature 328:221–227
Sieghart W (1989) Multiplicity of GABAA-benzodiazepine receptors. TIPS 10:407–411
Smirne S, Ferini-Strambi L, Pirola R, Tancredi O, Franceschi M, Pinto P, Bareggi SR (1989) Effects of flunitrazepam on cognitive functions. Psychopharmacology 98:251–256
Stanley RO, Tiller JWG, Adrian J (1987) The psychomotor effects of single and repeated doses of hypnotic benzodiazepines. Int Clin Psychopharmacol 2:317–323
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ingum, J., Bjørklund, R., Bjørneboe, A. et al. Relationship between drug plasma concentrations and psychomotor performance after single doses of ethanol and benzodiazepines. Psychopharmacology 107, 11–17 (1992). https://doi.org/10.1007/BF02244959
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244959