(-)-Lobeline hydrochloride

(-)-Lobeline hydrochloride is a modulator of nicotinic acetylcholine receptors (nAChRs) with various binding affinity. It displays very low affinity (Ki > 10000nM) for α7 receptors, but high affinity for rodent and human α4β2 receptors (Ki=1.4-2 nM). ^[1] It inhibits α7 nAChRs with an IC₅₀ value of 8.5 µM. ^[2]

nAChRs are composed of different subunits, and multiple populations of  nAChRs exist; brain nAChRs are primarily of the α4β2 and α7 type. ^[1]

In vitro, clastogenicity of lobeline and possible interactions between lobeline and ethyl alcohol were investigated in a mutagen-sensitivity assay on cultures of human lymphoblastoid cell lines. Lobeline alone was not clastogenic, but there was a marked increase in genetic damage resulting from a coclastogenic interaction between lobeline and ethyl alcohol. ^[5]

In vivo, male C57BL/6J mice were individually housed and acclimatized to 10% alcohol. Lobeline is a partial nicotinic agonist that attenuates alcohol consumption and preference in male C57BL/6J mice. ^[3] CF-1 male mice received an intraperitoneal injection of lobeline (5 or 10mg/kg). Lobeline did not show genotoxic or mutagenic effects and did not increase the ethanol-induced genotoxic effects in blood. Lobeline also protected blood cells against oxidative damage induced by hydrogen peroxide. ^[4]

Reference:

1. Flammia D1, Dukat M, Damaj MI, et al. Lobeline: structure-affinity investigation of nicotinic acetylcholinergic receptor binding. J Med Chem. 1999 Sep 9; 42 (18):3726-31.

2. Briggs CA, McKenna DG. Activation and inhibition of the human alpha7 nicotinic acetylcholine receptor by agonists. Neuropharmacology. 1998 Sep; 37 (9):1095-102.

3. Farook JM, Lewis B, Gaddis JG, et al. Lobeline, a nicotinic partial agonist attenuates alcohol consumption and preference in male C57BL/6J mice. Physiol Behav. 2009 Jun 22; 97 (3-4):503-6.

4. da Costa E Silva LD, Rodrigues LC¹, Dos Santos VR^1.et al. Evaluation of mutagenic and genotoxic activities of lobeline and its modulation on genomic instability induced by ethanol. Life Sci. 2014 May 17; 103 (2):73-8.

5. Brown NM, Trizna Z, Pathak S. Clastogenic interactions between lobeline sulfate and ethyl alcohol: a cytogenetic study. Anticancer Res. 1992 Sep-Oct; 12 (5):1467-9.