Laine-Cessac P, Turcant A, Premel-Cabic A, Boyer J, Allain P
Laboratoire de Pharmacologie et Toxicologie, Centre Hospitalier Universitaire, Angers, France.
Res Commun Chem Pathol Pharmacol. 1993 Feb;79(2):185-93.
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).
许多研究表明，组胺2受体拮抗剂（H2RA）具有体外抗胆碱酯酶作用，但已发表结果中关于这种抑制作用的类型和效力存在差异。此外，接受H2RA治疗的患者尚未显示出胆碱酯酶抑制作用。这些差异促使我们比较雷尼替丁、西咪替丁、尼扎替丁与吡啶斯的明的体外抗丁酰胆碱酯酶和体外抗乙酰胆碱酯酶活性。在6例患者持续静脉输注（150或200mg/d）雷尼替丁之前和期间，测量其血浆胆碱酯酶活性（PCEA）、红细胞胆碱酯酶活性（ECEA）和血浆雷尼替丁水平。我们的体外研究结果证实了H2RA的弱抗胆碱酯酶活性。雷尼替丁是丁酰胆碱酯酶最有效的抑制剂（Ki = 61μM）。雷尼替丁和尼扎替丁是乙酰胆碱酯酶最有效的抑制剂（Ki'分别为2.1μM、5.1μM），但效力比吡啶斯的明低一千倍（Ki = 0.003μM）。患者的研究结果显示，在输注雷尼替丁之前和期间测量的PCEA和ECEA之间无统计学显著差异（血浆雷尼替丁水平在0.31至1.25μM之间）。
