(-)-Lobeline hydrochloride

Nicotinic acetylcholine receptors (nAChRs) are important neuromodulatory cation channels which short-circuit their assimilating membrane by their primary endogenous agonist acetylcholine (ACh)¹. nAChRs are highly expressed in myocytes and neurons and are comprised of at least 17 studied subunits, that can be classified into two types: α (α1 – α10) and non-α (β1-4, γ, δ and ε). Various nAChR subunits co-assemble to create muscular (α1β1γδ and α1β1εδ) and neuronal channels which are found in different and more restrictive combinations (α2-6 and β2-4 possible arrangements, e.g. α4β2)^2,3.

Lobeline hydrochloride is a lipophylic alkaloid which either agonizes or antagonizes the nicotine-evoked response of nAChRs. Lobeline acts as an anxiolytic, a cognition enhancer and a neurotransmitter-release stimulant in the CNS, whereas it inhibits the response to ACh at the α7 subunit with an IC₅₀ of 8.5 μM, and decreases the endplate potential at the neuromuscular junction - thus attenuates locomotor sensitization^4-7. Moreover, its high affinity (K_i = 4-20 nM) to the α4β2, nAChR subtype, along with a nonselective binding to monoamine transporters, renders it capable of preventing the psychostimulatory effects of drugs of abuse⁸.