Tofisopam, a novel 3,4,-benzodiazepine: Multiple-dose effects on psychomotor skills and memory. Comparison with diazepam and interactions with ethanol

Abstract

Twelve healthy male volunteers were treated (double-blind crossover design) with tofisopam (a new 3,4-benzodiazepine), diazepam, or placebo, on 2 consecutive days each. Psychomotor skills were impaired after a single dose of diazepam (10 mg) given on day 1. Measurements on day 2 showed that some tolerance had developed to the diazepam-induced impairment of reactive and coordinative skills, but not to its effects on flicker fusion or on the extraocular muscle balance. Tofisopam failed to impair performance both as a single dose (100 mg) and after repeated doses (100 + 50 + 50 + 100 mg). The subjects felt more fatigue, dizziness, calmness, and passiveness after diazepam than after tofisopam. When either drug was given together with 0.8 g/kg ethanol on day 2, the breath ethanol concentrations were 0.7--1.0 mg/ml and all psychomotor skills were impaired. Diazepam + ethanol particularly impaired memory and learning as well. After this combination the subjects were classified (time anticipation test) as 'disqualified drivers' more often than after placebo. It is concluded that diazepam, as well as either benzodiazepine with ethanol, may reduce the ability to drive vehicles or operate machinery.

Central effects during the continuous osmotic infusion of a benzodiazepine (triazolam).

“…Some degree of tolerance or adaptation to the central effects of benzodiazepines may develop either with single doses of drugs which are slowly eliminated (Greenblatt et al, 1979) or with repetitive ingestion (Mattila et al, 1978;Church & Johnson, 1979;Seppala et al, 1980). However, there is limited information on the processes involved, and it is in this context that we have assessed psychomotor function during relatively constant plasma concentrations of a rapidly inactivated benzodiazepine, triazolam.…”

Development of two charge transfer complex spectrophotometric methods for determination of tofisopam in tablet dosage form

“…However, tofisopam does not have anticonvulsant, calming [1], skeletal-tension reduction, motor skill-damaging or amnestic [2] effects [3]. It is prescribed for the therapy of worry and alcohol retraction, in a dose of 50 -300 mg daily divided into three doses.…”

Development of Two Charge-Transfer Complex Spectrophotometric Methods for Determination of Tofisopam in Tablet Dosage Form

“…However, tofisopam does not have anticonvulsant, calming [1], skeletal reduce tension, motor skill-damaging or amnestic [2] features ( Figure 1) [3]. Tofisopam is used for the therapy of worry and alcohol retraction, and is prescribed in a dose of 50 -300 mg daily, separated into three doses.…”