Comparison of the Myotonolytic Activity of Tizanidine,Eperisone and Afloqualone in Mouse and Rabbit

Abstract

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.