Predictive value of muscle relaxant models in rats and cats

A number of clinically effective muscle relaxants and structurally related compounds were examined in three animal models of muscle relaxant activity in order to determine the utility of these models in predicting clinical activity. The methods used were attenuation of morphine-induced rigidity in rats, decerebrate rigidity in cats, and the polysynaptic linguomandibular reflex in cats. Specificity of the compounds was assessed by comparing these data to the ability of the compounds to induce rotarod failure in rats and to inhibit the monosynaptic patellar reflex in cats. Diazepam and chlordiazepoxide were of limited potency in morphine-induced rigidity and decerebrate rigidity, but were potent on the polysynaptic reflex. Mephenesin, cyclobenzaprine, and the newer benzodiazepine, midazolam, were effective and moderately specific in all three models. Baclofen and dantrolene were effective but were of little or no specificity in all models. Analysis of the data yielded poor correlation between clinical muscle relaxant potency and the potencies obtained in these animal models. The correlation coefficients of 0.54, 0.50, and 0.70 for the linguomandibular reflex, decerebrate rigidity, and morphine rigidity, respectively, were not statistically significant, in contrast with a coefficient of 1.0 using previously reported data on these compounds in inhibiting morphine-induced Straub tail in mice. Thus, the three models used in this study may possess utility in the study of sites and mechanisms of action and structure-activity relationships of potential muscle relaxants, but they do not appear to be as useful as morphine-induced Straub tail in potency comparisons between different chemical classes.