Inhibition of cholinesterases by histamine 2 receptor antagonist drugs

Many studies have demonstrated that histamine 2 receptor antagonists (H2RA) have in vitro anticholinesterase effects, but discrepancies about type and potency of this inhibitory effect exist among published results. Moreover, cholinesterase inhibition has not been shown in patients receiving H2RA. These discrepancies led us to study the in vitro antibutyryl- and in vitro antiacetylcholinesterase activities of ranitidine, cimetidine, nizatidine comparatively to pyridostigmines. Plasma cholinesterase activity (PCEA), erythrocyte cholinesterase activity (ECEA) and plasma ranitidine levels were measured in six patients before and during continuous IV infusion (150 or 200 mg/d) of ranitidine. Our in vitro results confirm the weak anticholinesterase activity of H2RA. Ranitidine is the most potent inhibitor of butyrylcholinesterase (Ki = 61 microM). Ranitidine and nizatidine are the most potent inhibitors of acetylcholinesterase (Ki' = 2.1 microM, Ki' = 5.1 microM, respectively) but one thousand times less effective than pyridostigmine (Ki = 0.003 microM). The results in patients show no statistically significant difference between PCEA and ECEA measured before and during ranitidine infusion (plasma ranitidine levels between 0.31 and 1.25 microM).