Palmitoyl serotonin is a hybrid molecule patterned after arachidonoyl serotonin, antagonist of FAAH. Palmitoyl serotonin inhibits L-3,4-dihydroxyphenylalanine (HY-N0304) induced abnormal involuntary movements. Palmitoyl serotonin has the potential for the research of parkinson's disease (PD)[1][2].
ChEBI: N-palmitoylserotonin is an N-acylserotonin obtained by formal condensation of the carboxy group of hexadecanoic acid with the primary amino group of serotonin. It is functionally related to a hexadecanoic acid.
palmitoyl serotonin is a trpv1 antagonist with ic50 value of 0.76 μm for human trpv1 [1].the transient receptor potential vanilloid-type 1 (trpv1) channel is a nonselective cation channel that may be activated by a variety of exogenous and endogenous physical and chemical stimuli. trpv1 is decreased in the injured nerve fibers but increased in those proximal to the site damage. trpv1 is a potential new target for the development of analgesic and anti-inflammatory drugs [1].palmitoyl serotonin is a hybrid molecule patterned after arachidonoyl serotonin. arachidonoyl serotonin is a dual antagonist of trpv1 and fatty acid amide hydrolase (faah) with ic50 values of 0.27 and 8 μm, respectively. arachidonoyl serotonin was highly effective against both acute and chronic peripheral pain [1][2]. in trpv1 and faah assays, palmitoyl serotonin inhibited anandamide hydrolysis mediated by faah and capsaicin-induced intracellular ca2+ elevation in hek293 cells overexpressing the human recombinant trpv1 receptor with ic50 values of > 50 μm and 0.76 μm, respectively. however, the effects of replacing the arachidonoyl portion with the saturated 16-carbon palmitoyl moiety had not been studied [1].
Palmitoyl serotonin (0.3 mg/kg; daily for 10 days) effectively attenuates the development of L-DOPA-induced dyskinesia (LID) and increases of ERK1/2 phosphorylation and FosB/ΔFosB expression in the hemi-parkinsonian mouse model[1].
| Animal Model: | 25-28 g, Eight-week-old male C57BL/6J mice ( 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian mouse model)[1] |
| Dosage: | 0.3 mg/kg |
| Administration: | daily for 10 days |
| Result: | Reduced axial, limb, and locomotive AIM scores on day 10, suppressed the hyper-phosphorylation of ERK1/2 in the 6-OHDA-lesioned striatum, suppressed the overexpression of FosB and ΔFosB in the 6-OHDA-lesioned striatum. |
[1]. ortar g, cascio mg, de petrocellis l, et al. new n-arachidonoylserotonin analogues with potential "dual" mechanism of action against pain. j med chem. 2007 dec 27;50(26):6554-69.
[2]. maione s, de petrocellis l, de novellis v, et al. analgesic actions of n-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid trpv1 receptors. br j pharmacol. 2007 mar;150(6):766-81.
