Brainstem noradrenergic system depression by cyclobenzaprine

A possible mechanism for CBZ's depressant action on the brainstem noradrenergic system was investigated in precollicularly decerebrated cats immobilized with Flaxedil (2 mg/kg, i.V.). Phenoxybenzamine (2 mg/kg, i.v.) was consistently observed to antagonize CBZ's suppression of both the flexor and extensor MSRs. Subsequent evidence for the brainstem noradrenergic system mediating the CBZ effect was established by extracellular recordings. Unitary discharges of LC neurons identified histologically were demonstrated to be inhibited chiefly by CBZ (1 mg/kg, i.V.). In some instances, the inhibition of spontaneous coerulear activity was found to parallel temporally the MSR response following CBZ administration. Coerulospinal neurons characterized by physiological criteria also revealed diminished activities following CBZ (0.5 mg/kg, i.V.). A decreased neuronal somatic excitability was also observed by the antidromically driven coerulospinal neurons following CBZ. It is concluded that CBZ's depressant action is mediated, at least in part, by the noradrenergic coerulospinal system. Other possible mechanisms of CBZ action are also discussed.