TMPH hydrochloride is a potent inhibitor of neuronal AChRs. Evaluation of AChR subunits expressed in Xenopus laevis oocytes indicated that TMPH can produce a potent and long-lasting inhibition of neuronal AChR formed by the pairwise combination of the most abundant neuronal α (i.e., α3 and α4) and β subunits (β2 and β4), with relatively little effect, because of rapid reversibility of inhibition, on muscle-type (α1β1γδ) or α7 receptors. However, the inhibition of neuronal β subunit-containing receptors was also decreased if any of the nonessential subunits α5, α6, or β3 were coexpressed. This decrease in inhibition is shown to be associated with a single amino acid present in the second transmembrane domain of these subunits. TMPH ability to relate the diverse central nervous system effects to specific AChR subtypes makes it a helpful tool for studying the functional roles of AChR.
