Discriminative stimulus properties of alprazolam
by
Gommans J, Hijzen TH, Maes RA, Olivier B
Department of Psychopharmacology,
Faculty of Pharmacy,
Universiteit Utrecht,
Sorbonnelaan 16,
3584 CA Utrecht, The Netherlands
Psychopharmacology (Berl) 2000 Feb 4; 148(2):146-152
ABSTRACT
Rationale: The triazolobenzodiazepine alprazolam has a unique clinical
profile compared to most other benzodiazepines (e.g. diazepam,
chlordiazepoxide), in that it is used to treat panic disorder and is effective
in depression, two disorders that are usually treated with anti-depressants.
Previous drug discrimination studies suggested that alprazolam has stimulus
properties in common with antidepressants. Objective: In the present study, the
discriminative stimulus properties of alprazolam were investigated to test more
conclusively the role of benzodiazepine receptors and whether alprazolam has
stimulus properties in common with antidepressants. Methods: Male Wistar rats
(n=12) were trained to discriminate between alprazolam (2.0 mg/kg, PO) and
vehicle in an operant two-lever drug discrimination procedure under a tandem
VI40"-FR10 schedule of reinforcement. Generalization and antagonism tests were
carried out under 2 min extinction. Results: In generalization tests, a number
of benzodiazepines (alprazolam, chlordiazepoxide, midazolam, lorazepam) and the
barbiturate pentobarbital substituted completely, while zolpidem and abecarnil
substituted partially for alprazolam. In contrast, no significant degree of
generalization to the antidepressants imipramine and fluvoxamine and the
putative antidepressants buspirone and flesinoxan was found. In antagonism
studies alprazolam could be antagonized (almost) completely by flumazenil,
partially by pentylenetetrazole, but not by methyl
6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM),
N-methyl-beta-carboline-3-carboxamide (FG-7142) and picrotoxin. Conclusions:
These results show that the discriminative stimulus properties of alprazolam are
mediated by benzodiazepine receptors and that the finding that antidepressants
share discriminative stimulus effects with alprazolam may have limited
generality.
Xanax
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Valerian
Gepirone
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Beta-blockers
Benzodiazepines
Future anxiolytics
Drug-induced mania
Low-dose alprazolam
Long-term alprazolam
Alprazolam : structure
Alprazolam and risk-taking
Anxiolytics/antidepressants
Alprazolam and panic disorder
Alprazolam-induced hypomania
Alprazolam (Xanax) plus heroin
Opipramol (Insdon) v alprazolam (Xanax) for GAD
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