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Comparison of the spectrum of cognitive effects of alprazolam and adinazolam after single doses in healthy subjects
Authors:J. C. Fleishaker  P. D. Garzone  J. H. Chambers  K. Sirocco  H. Weingartner
Affiliation:(1) Clinical Pharmacokinetics Unit, The Upjohn Company, 49007 Kalamazoo, MI, USA;(2) Center for Pharmacodynamic Research, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pa., USA;(3) National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md., USA;(4) Present address: Genetics Institute, Cambridge, Mas., USA
Abstract:Single doses of alprazolam (0, 0.5, 1.5 mg) or adinazolam mesylate sustained release tablets (SR) (0, 15, 45 mg) were administered to separate groups of 12 healthy men in a crossover design. Psychomotor performance was assessed by digit symbol substitution (DSST), and memory was assessed using a test battery which reflects various aspects of memory, including attention/working memory, explicit memory (recall of categorically related words), semantic memory (fragmented picture recognition, generation of category exemplars), and implicit memory (time saved in resolving fragmented pictures on the second exposure). Maximal psychomotor performance and memory decrements for the highest active doses were significantly different from placebo for all tasks at some time after dosing. The maximum decrement in DSST was not significantly different between drugs at the high dose (P=0.288). Maximum attention/working memory decrements were significantly different between the high doses of the active compounds (P=0.031), and the difference in maximum category recall decrement was marginally significant (P=0.067). Access to knowledge memory was not significantly altered by these drugs; these results are similar to those obtained for other benzodiazepines. Both drugs exhibited slight effects on implicit memory. The results suggest that the sedative and memory effects of these triazolobenzodiazepines may not be closely related and suggest that adinazolam has a somewhat different spectrum of cognitive effects relative to alprazolam.
Keywords:Triazolobenzodiazepine  Psychomotor performance  Memory  Active metabolite  Cognition
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