Anticonflict and rotarod impairing effects of alprazolam and diazepam in rat after acute and subchronic administration. 1989

B Söderpalm, and E Eriksson, and J A Engel
Department of Pharmacology, University of Göteborg, Sweden.

1. The anticonflict and the rotarod impairing effects of the triazolo-benzodiazepine alprazolam (APZ) and the conventional 1,4-benzodiazepine (BDZ) diazepam (DIZ) were studied in the rat. 2. After acute administration the two drugs displayed approximately equal potency with respect to anticonflict effects in Vogel's conflict test and in Montgomery's conflict test. The results obtained in the former model indicate that also the efficacies of the two drugs are approximately equal. The shapes of the dose response curves obtained in this model differed, however, markedly. Thus, while APZ displayed a wide high efficacy dose-range (0.5-16.0 mg/kg), a maximal effect of DIZ was obtained in a narrow dose-range only (around 4.0 mg/kg). 3. Acutely, APZ was more rotarod impairing than DIZ; total impairment after 2.0 mg/kg of APZ and 3.5 mg/kg of DIZ. 4. After daily treatment with doses producing approximately equal and close to maximal anticonflict effects (APZ 1.25 mg/kg/day; DIZ 3.0 mg/kg/day) tolerance developed to the rotarod impairing (6 days of treatment) and the anticonflict (Vogel's conflict test; 9 days of treatment) effects of both drugs. It appeared, however, as if tolerance was more pronounced to the ataxic/sedative effects (approximately a four-fold rightward shift of the dose-response curve) than to the anticonflict effect (approximately a two-fold shift) of APZ, whereas tolerance developed to about the same extent to the two effects of DIZ (approximately two-fold shifts). 5. In conclusion, for APZ, but not for DIZ, after long-term administration of a dose producing marked anxiolytic-like effects, the relationship anxiolytic-like effect vs. ataxic/sedative effects was altered. These findings offer a tentative explanation to the putative advantage of APZ over conventional BDZs in the treatment of panic disorder.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D008297 Male Males
D009042 Motivation Those factors which cause an organism to behave or act in either a goal-seeking or satisfying manner. They may be influenced by physiological drives or by external stimuli. Incentives,Disincentives,Expectations,Disincentive,Expectation,Incentive,Motivations
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D003220 Conflict, Psychological The internal individual struggle resulting from incompatible or opposing needs, drives, or external and internal demands. In group interactions, competitive or opposing action of incompatibles: antagonistic state or action (as of divergent ideas, interests, or persons). (from Merriam-Webster's Collegiate Dictionary, 10th ed) Conflict, Psychology,Psychological Conflict,Psychological Conflicts
D003975 Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D000525 Alprazolam A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of PANIC DISORDERS, with or without AGORAPHOBIA, and in generalized ANXIETY DISORDERS. (From AMA Drug Evaluations Annual, 1994, p238) Alprazolan,Alprox,Apo-Alpraz,Cassadan,D-65MT,Esparon,Kalma,Novo-Alprazol,Nu-Alpraz,Ralozam,Tafil,Trankimazin,U-31,889,Xanax,Apo Alpraz,D65MT,Novo Alprazol,Nu Alpraz,U31,889
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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