Afloqualone

Accidental afloqualone intoxication in two dogs

Two dogs presented to the emergency service after accidental ingestion of afloqualone tablets, a muscle relaxant used for back pain in humans. Toxic effects of the drug in these dogs included vomiting, respiratory depression, seizures, ataxia, bradycardia, and hematuria. Treatment consisted of fluid diuresis, furosemide, and propofol. Flumazenil, a gamma-amino butyric acid antagonist, was administered intravenously; however, it was not effective in stopping the seizures in these dogs. Both dogs recovered with supportive treatment. To the authors' knowledge, this is the first documented report of afloqualone intoxication in dogs.

Coma and seizure caused by an afloqualone overdose

Comparative effects on psychomotor performance of the muscle relaxant afloqualone, alone and with ethanol

The purpose of this study was to investigate the interaction between 40 mg afloqualone, a new centrally acting muscle relaxant and 0.5 g/kg ethanol using a double-blind three-way cross-over trial in which subjects were each given afloqualone with ethanol, ethanol alone and afloqualone alone. We first compared the effects of 40 mg oral afloqualone and 15 mg diazepam (considered as a reference drug) on the psychomotor and cognitive performance and muscular relaxation of 12 healthy male volunteers. Performance was assessed by six objective tests and eight visual analogue self-rating scales. All the above treatments were separated by a 2-week interval. Volunteers performed the objective tests 1 h after drug ingestion, and the self-rating scale evaluations before drug intake and 1, 3.5, 6 and 8 h thereafter. Afloqualone impaired psychomotor performance less than diazepam as shown by the number of correct answers in the digit symbol cancellation test and the time needed to complete this test. However, the measurement of the frontalis muscle action potential showed that the muscle relaxant activity of 40 mg afloqualone was equivalent to that of 15 mg diazepam. Furthermore, afloqualone given at an effective relaxant dose did not enhance the effects of a single dose of ethanol which predominated on either psychomotor performance or subjective feelings.

Determination of afloqualone in human plasma using liquid chromatography/tandem mass spectrometry: Application to pharmacokinetic studies in humans

Two methods for determining the central-acting muscle relaxant afloqualone in human plasma were developed and compared using API2000 and API4000 liquid chromatography tandem mass spectrometry (LC/MS/MS) systems. In the API2000 LC/MS/MS system, afloqualone and the internal standard methaqualone were extracted from plasma using a methyl-tertiary ether. After drying the organic layer, the residue was reconstituted in a mobile phase (0.1% formic acid-acetonitrile:0.1% formic acid buffer, 80:20 v/v) and injected onto a reversed-phase C(18) column. The isocratic mobile phase was eluted at 0.2ml/min. The ion transitions monitored in multiple reaction-monitoring mode were m/z 284-->146 and 251-->117 for afloqualone and methaqualone, respectively. Sample preparation for the API4000LC/MS/MS system involved simple protein precipitation with an organic mixture (methanol:10% ZnSO(4)=8:2). The ion transitions monitored in multiple reaction-monitoring mode were m/z 284-->146 and 251-->131 for afloqualone and methaqualone, respectively. In both assays, the coefficient of variation of the precision was less than 11.8%, the accuracy exceeded 91.5%, the limit of quantification was 0.5ng/ml, and the limit of detection was 0.1ng/ml for afloqualone. Two methods were used to measure the plasma afloqualone concentration in healthy subjects after a single oral 20-mg dose of afloqualone. During subsequent application of the methods, we observed that high-concentration plasma samples (>7ng/ml) prepared using the protein precipitation method resulted in about 20% higher afloqualone concentrations than with plasma samples prepared using the liquid-liquid extraction method. We believe that this phenomenon was related to the cleanness of the sample and its chemical nature.

Comparison of the myotonolytic activity of tizanidine, eperisone and afloqualone in mouse and rabbit

The central muscle relaxant activity of the antispastic agent tizanidine was compared with that of two novel clinical agents, afloqualone and eperisone, in the mouse and rabbit. Oral tizanidine strongly inhibited morphine-elicited Straub tail induction in the mouse, showing a median effective dose (ED50) of 1.2 mg/kg. Intravenous tizanidine also inhibited hind limb extensor reflex activity in the rabbit with an ED50 of 0.02 mg/kg. Afloqualone and eperisone, however, were much weaker in the mouse assay with ED50 values of 8.2 and 58.1 mg/kg, respectively. At respective intravenous doses of 2.0 and 1.0 mg/kg, afloqualone and eperisone caused maximally 32% and 41% inhibition of reflex activity in the rabbit. On this basis, afloqualone might be expected to exhibit moderate myotonolytic activity in rheumatological indications, but to be of questionable value in spasticity. Similarly, clinical myotonolytic activity of eperisone would only be expected at high doses unless its functional bioavailability were to be much better in man than in either the mouse or rabbit.