Increase of ?antianxiety? activity and tolerance of behavioral depression during chronic administration of oxazepam

Margules, David L.; Stein, Larry

doi:10.1007/bf00401620

Cited by 232 publications

(35 citation statements)

References 4 publications

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“…We observed that tolerance to the anticonflict activity of diazepam did not develop, which is similar to the results reported by Margules and Stein (15). Furthermore, SM-3997 also exhibited the anticonflict activity following 5 or 10 daily administrations as well as single adminis tration.…”

Section: Discussionsupporting

confidence: 90%

Pharmacological properties of SM-3997: A new anxioselective anxiolytic candidate.

et al. 1987

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Abstract-Pharmacologicalproperties of SM-3997 (3aa,4Q,7(9,7aa-hexahydro-2 (4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-4,7-methano-1 H-isoindole-1,3(2H) dione dihydrogen citrate) have been examined in rats and mice. SM-3997 showed a dose-related anticonflict activity in rats in a water lick conflict paradigm, and it had no effect on water consumption in a spontaneous water drinking test. The potency of SM-3997 appeared to be equal to that of buspirone and about one-half that of diazepam.No tolerance to the anticonflict activity of SM-3997 was observed following 5 and 10 consecutive days of treatment. Unlike diazepam, SM-3997 had no anticonvulsant effect and had very weak muscle relaxant and hypnotic effects.On the other hand, SM-3997 and buspirone exhibited dopamine antagonistic action, although the potency of SM-3997 was less than one fourth that of buspirone.These results show that SM-3997 is a new anxioselective anxiolytic agent which is weaker than buspirone in the dopaminergic neuron system.

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Section: Discussionsupporting

confidence: 90%

Pharmacological properties of SM-3997: A new anxioselective anxiolytic candidate.

et al. 1987

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“…The rats were all 'drug-sophisticated' that is, they had been dosed previously with various benzodia zepine derivatives on a weekly basis for several months. In fact, Margules and Stein (11) have shown that response to Geller's test is more constant in 'drug-sophisticated' than in 'drug-naive' rats.…”

Section: Drugsmentioning

confidence: 99%

Central Effects of Three Fluorinated Benzodiazepines in Comparison with Diazepam

Babbini¹,

Torrielli²,

Gaiardi³

et al. 1974

Pharmacology

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The central effects of the 5-(o-fluorophenyl)-3-hydroxybenzodiazepines SAS 643, SAS 646 and Ro 7–5205 were investigated and compared with those of diazepam. It was found that, in rats, these drugs have a pharmacological profile very close to that of diazepam. They possessed a high antimetrazol activity, a muscle-relaxant effect and a depressive action upon exploratory behavior. Moreover, they facilitated behavior suppressed by punishment and caused a synchronization of the EEG pattern. With regard to the relative potencies of the compounds, SAS 646 was found to be the most potent drug by far; it was 4–10 times more potent than diazepam, while SAS 643 was equipotent to the latter. This suggests the usefulness of the new compounds for clinical use. The structure-activity relationships indicate that the general rules stated by Stembach et al are valid also for the group of the 5-(O-fluorophenyl)-3-hydroxybenzodiazepines.

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“…Owing to the presence of a punished and a unpunished schedule the unspecific sedative properties and the specific anxiety-reducing action of the drug can be measured in the same animal. However, a strong enough sedative activity could mask the antianxiety effect, and Margules and Stein (14) suggest a chronic dosing, the sedative action, not the antianxiety one undergoing tolerance. In the present study we found that lorazepam can induce a significant increase of lever pressing during the punished schedule in spite of its strong depressive effect which lowers operant behavior during the unpunished schedule (see fig.…”

Section: Discussionmentioning

confidence: 99%

Influence of N<sub>1</sub>-2-Hydroxyethyl Substitution on Central Activity of Oxazepam and Lorazepam

Babbini¹,

Torrielli²,

Gaiardi³

et al. 1973

Pharmacology

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The central activities of two N₁-2-hy droxyethyl substituted derivatives of oxazepam and lorazepam (SAS 602 and SAS 632, respectively) were compared with those of the parent compounds. It was found that in rats all the drugs had antimetrazol activity and produced muscle relaxant effects and depressive ac tions upon exploratory behavior. They were all active in facilitating behavior suppressed by punishment, and caused a synchronization of the EEG pattern lasting 4–5 h. Both N₁-2-hydroxyethyl substituted compounds showed a reduced potency when compared with oxazepam and lorazepam. Compound SAS 632, however, was more active than oxazepam in conflict behavior, with less muscle relaxant activity. This could suggest a usefulness of the compound for clinical use.

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Increase of ?antianxiety? activity and tolerance of behavioral depression during chronic administration of oxazepam

Cited by 232 publications

References 4 publications

Pharmacological properties of SM-3997: A new anxioselective anxiolytic candidate.

Pharmacological properties of SM-3997: A new anxioselective anxiolytic candidate.

Central Effects of Three Fluorinated Benzodiazepines in Comparison with Diazepam

Influence of N<sub>1</sub>-2-Hydroxyethyl Substitution on Central Activity of Oxazepam and Lorazepam

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