Neuropharmacology. 1984 Aug;23(8):947-53.
Cyclobenzaprine: effect on tonic vibration reflexes in local tetanus cat preparations.

Share NN.

Local tetanus was induced by the injection of toxin into the gastrocnemius-soleus muscle of cats. After 48 hr, longitudinal vibration of the muscle was used to elicit a reflex contraction (tonic vibration reflex, TVR). In other experiments, electrical stimulation of various regions of the central nervous system served to elicit contraction of the muscle alone or to facilitate a vibration (150 mu at 300 Hz)-induced tonic vibration reflex. In contrast with normal animals, tonic vibration reflex responses in local tetanus preparations of decerebrate cats were augmented after transection of the spinal cord at Cl. In decerebrate local tetanus preparations, a dose-related reduction of tonic vibration reflex responses, induced at all frequencies and amplitudes of muscle vibration, was observed after doses of 0.5 to 3.5 mg/kg (i.v.) of cyclobenzaprine. Muscle contractions induced by stimulation of the medial reticular formation and facilitation of tonic vibration reflex responses were more sensitive to the action of cyclobenzaprine than were similar responses activated through stimulation of Deiters' lateral vestibular nucleus. In spinal preparations, tonic vibration reflex responses were only moderately reduced after similar doses of cyclobenzaprine. Contractions induced by stimulation of the spinal cord (T6) and facilitated tonic vibration reflex responses were only moderately reduced, whereas the post-stimulus-induced facilitations were considerably attenuated. Thus, experiments in local tetanus preparations support further the concept that the major site of action of cyclobenzaprine is supraspinal, whereas its action upon spinal structures contributes to its overall skeletal muscle-relaxant activity.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6483119&dopt=Abstract cyclobenzaprine Flexeril





Life Sci. 1983 Oct 24;33(17):1727-30.
Amitriptyline sensitization of a serotonin-mediated behavior depends on the passage of time and not repeated treatment.

Antelman SM, DeGiovanni LA, Kocan D, Perel JM, Chiodo LA.

Daily treatment for 10 days with either amitriptyline or the tricyclic muscle relaxant, cyclobenzaprine, increased the incidence of head-twitch behavior in response to 5-hydroxytryptophan (5-HTP) when this was examined two days later. Only one day of amitriptyline treatment followed by an 11-day hiatus before administration of 5-HTP also sensitized the head-twitch response whereas similar amitriptyline treatment followed by 5-HTP one hour later failed to do so. These data provide the first evidence for time-dependent sensitization of brain serotonin systems.

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J Pharmacol Methods. 1983 Nov;10(3):175-83.
Predictive value of muscle relaxant models in rats and cats.

Novack GD, Zwolshen JM.

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.

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Biochem Biophys Res Commun. 1984 Jun 29;121(3):749-54.
Reduction of tertiary amine N-oxides by liver preparations: function of aldehyde oxidase as a major N-oxide reductase.

Kitamura S, Tatsumi K.

Reduction of tertiary amine N-oxides to the corresponding amines by liver preparations was investigated with imipramine N-oxide and cyclobenzaprine N-oxide under anaerobic conditions. Rabbit liver cytosol in the presence of an electron donor of aldehyde oxidase exhibited a significant N-oxide reductase activity which is comparable to the activity of the liver microsomes supplemented with NADPH. Rabbit liver aldehyde oxidase also exhibited the N-oxide reductase activity in the presence of its electron donor, indicating that the activity observed in the liver cytosol is due to this cytosolic enzyme. Furthermore, the tertiary amine N-oxide reductase activity of liver cytosols from rats, mice, hamsters and hogs was demonstrated by comparison with that of liver microsomes from these mammalian species.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6743317&dopt=Abstract cyclobenzaprine Flexeril