**Background**
Nicotinic acetylcholine receptors (nAChRs) are a class of ligand-gated ion channels that play critical roles in both the central and peripheral nervous systems, as well as in modulating immune responses. Among these, the $\alpha3\beta2$ and $\alpha3\beta4$ subtypes are of particular interest due to their involvement in various physiological processes, including metabolic regulation and inflammatory responses. Targeting these receptors provides a potential therapeutic avenue for treating metabolic disorders and autoimmune conditions. In this context, we will introduce an anthelmintic agent with immunomodulatory properties – Levamisole.
**Definition**
Levamisole is an immunomodulatory agent that acts as a positive allosteric modulator (PAM) for the $\alpha3\beta2$ (EC$_{50}$ = 300 $\mu$M) and $\alpha3\beta4$ (EC$_{50}$ = 100 $\mu$M) subtypes of nAChRs.
**In Vitro and In Vivo Studies**
The Levamisole description highlights its utility as an orally active compound with a molecular weight of 204.30 and the chemical formula C$_{11}$H$_{12}$N$_{2}$S. Regarding Levamisole biological activity, in vitro cytotoxicity assays have been conducted across various human and mouse cell lines. In human HeLa cells, Levamisole exhibited IC$_{50}$ values of 250 $\mu$M (72 h, Coulter counting method) and 96 $\mu$M (24 h, MTT assay). In other cell lines, the IC$_{50}$ was found to be > 100 $\mu$M for A549 and MCF7 cells (24 h, MTT assay), > 250 $\mu$M for CCRF-CEM cells (72 h, Coulter counting method), and 206 $\mu$M for mouse L1210 cells (48 h, Coulter counting method).
Furthermore, Levamisole in vivo studies have demonstrated its potential in metabolic research. Specifically, the administration of (S)-(-)-Levamisole at doses of 50 $\mu$g/ml and 200 $\mu$g/ml via oral gavage (p.o.) for 30 days was found to prevent weight gain in CD-1 mice fed a high-fat diet. These findings suggest that the modulation of $\alpha3\beta4$ nAChRs may play a role in regulating obesity and weight gain. In conclusion, Levamisole is a positive allosteric modulator of nAChRs with significant immunomodulatory and metabolic regulatory potential.
Keywords
Levamisole, 14769-73-4, (-)-Tetramisole, nAChR, Parasite, Nicotinic acetylcholine receptors, immunomodulatory, positive allosteric modulator, CD-1 Mice,α3β2 nAChR, Inhibitor, inhibitor, inhibit
References
[1] Lewis JA, et al. Levamisole: A Positive Allosteric Modulator for the α3β4 Nicotinic Acetylcholine Receptors Prevents Weight Gain in the CD-1 Mice on a High Fat Diet. Curr Pharm Des. 2017;23(12):1869-1872.
[2] Mehta KP, et al. Immunoregulatory treatment for minimal change nephrotic syndrome. Arch Dis Child. 1986;61(2):153-158.