Cyclobenzaprine HCl (Synonyms: MK-130)

Cyclobenzaprine is a 5-HT2 receptor antagonist and inhibitor, in some article, cyclobenzaprine hydrochloride was used as the compound to research in cyclobenzaprine. Cyclobenzaprine inhibits the enhancement of the monosynaptic reflex (MSR) induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Cyclobenzaprine strongly binds to 5-HT2 receptors with a Ki value of 62 nM. Cyclobenzaprine binds to 5-HT1 receptor with a Ki value of 2900 nM [1] [2].

5-HT2 receptors are G-protein coupled. They comprise three subtypes that are related in their amino acid sequence, molecular structure and signaling properties: 5-HT2A, 5-HT2B and 5-HT2C receptors. With widespread distribution in the central nervous system, 5-HT2A and 5-HT2C receptors function there. In the central nervous system, 5-HT2B receptors are restrictedly expressed [3].

In 16 of 21 spontaneously active neurons, the administration of cyclobenzaprine at 1 mg/kg decreased the discharge rate of neurons, while two neurons showed no response and three neurons demonstrated an increased rate. The decrease amount varied widely but was always ≥ 25%. In three cases, the decrease amounts were 100%. In all cases, the cell response to cyclobenzaprine followed the MSR response very closely in time [2].

After DOI treatment in rats, treatment with cyclobenzaprine increased the mono- and polysynaptic reflex amplitudes to about 150% of control level. In intact (nonspinalized) rats, the amplitude of mono- and polysynaptic reflex potentials were significantly reduced by cyclobenzaprine hydrochloride (300 µg/kg, i.v.). Within 15 min after the administration of cyclobenzaprine, the maximum effect was obtained, and this effect persisted for over 60 min. The mono- and polysynaptic reflex amplitudes were inhibited by cyclobenzaprine by about 20% and 40%, respectively. In intact rats, the depression of the mono- and polysynaptic reflex potentials induced by cyclobenzaprine hydrochloride (300 µg/kg, i.v.) was significantly inhibited by 5-HT depletion. 15 min after the administration of cyclobenzaprine in control rats, the mono- and polysynaptic reflex amplitudes were reduced to about 40–50% of the preadministration value [1].

References:
[1].  Honda M, Nishida T, Ono H. Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT2 receptors. European journal of pharmacology, 2003, 458(1): 91-99.
[2].  Barnes C D, Fung S J, Gintautas J. Brainstem noradrenergic system depression by cyclobenzaprine. Neuropharmacology, 1980, 19(2): 221-224.
[3].  Leysen J E. 5-HT2 receptors. Current Drug Targets-CNS & Neurological Disorders, 2004, 3(1): 11-26.