Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems

The centrally acting muscle relaxant cyclobenzaprine was thought to be an alpha(2)-adrenoceptor agonist that reduced muscle tone by decreasing the activity of descending noradrenergic neurons. In the present study, we examined the effects of cyclobenzaprine on descending neurons by measuring the monosynaptic reflex in rats. Cyclobenzaprine reduced the monosynaptic reflex amplitude dose dependently and this effect was not inhibited by the alpha(2)-adrenoceptor antagonists idazoxan and yohimbine. Cyclobenzaprine-induced monosynaptic reflex depression was not attenuated by noradrenergic neuronal lesions produced by 6-hydroxydopamine. However, cyclobenzaprine inhibited monosynaptic reflex facilitation induced by (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, a 5-HT2 receptor agonist, in spinalized rats markedly, and 5-HT depletion by DL-p-chlorophenylalanine inhibited the depressive effect of cyclobenzaprine on the monosynaptic reflex. These results suggest that cyclobenzaprine is a 5-HT2 receptor antagonist and that its muscle relaxant effect is due to inhibition of serotonergic, not noradrenergic, descending systems in the spinal cord.