Hyoscine butylbromide potently blocks human nicotinic acetylcholine receptors in SH-SY5Y cells

Hyoscine butylbromide (HBB; tradenames: Buscopan®/Buscapina®) is an antispasmodic drug for the treatment of abdominal pain associated with gastrointestinal cramping. As a hyoscine derivative, this compound competitively inhibits muscarinic acetylcholine (ACh) receptors on smooth muscle cells in the gastrointestinal tract. Preliminary investigations suggested that it might also inhibit nicotinic ACh receptors. This study investigated the effect of HBB on nicotinic ACh receptor-mediated membrane currents in SH-SY5Y cells. ACh and nicotine application-induced comparable membrane currents with EC50 values of 25.9 ± 0.6 and 40.1 ± 0.4 μM, respectively. When coapplied with 100 μM ACh, HBB concentration-dependently suppressed currents with an IC50 value of 0.19 ± 0.04 μM, and was approximately seven-times more potent than the ganglionic blocker, hexamethonium (IC50 = 1.3 ± 0.3 μM). Increasing the agonist concentration to 5 mM did not affect the amount of block by HBB, which suggests a non-competitive mode of action. These functional in vitro data demonstrate for the first time that HBB blocks neuronal nicotinic ACh receptors in the same concentration range as it inhibits muscarinic ACh receptors. If one hypothesizes that HBB might also affect nicotinic receptors in autonomic neurons in vivo (e. g. in the enteric nervous system), this effect could contribute to its spasmolytic activity.