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Nicotinic acetylcholine receptors (nAChRs) are important neuromodulatory cation channels which short-circuit their assimilating membrane by their primary endogenous agonist acetylcholine (ACh). nAChRs are highly expressed in myocytes and neurons and are comprised of at least 17 studied subunits, that can be classified into two types: (A) ((A)1 � (A)10) and non-(A) ((B)1-4, (G), (D) and ?). Various nAChR subunits co-assemble to create muscular ((A)1(B)1(G)(D) and (A)1(B)1?(D)) and neuronal channels which are found in different and more restrictive combinations ((A)2-6 and (B)2-4 possible arrangements, e.g. (A)4(B)2.
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 (A)7 subunit with an IC50 of 8.5 micro M, and decreases the endplate potential at the neuromuscular junction - thus attenuates locomotor sensitization. Moreover, its high affinity (Ki = 4-20 nM) to the (A)4(B)2, nAChR subtype, along with a nonselective binding to monoamine transporters, renders it capable of preventing the psychostimulatory effects of drugs of abuse.