Tomokane Yuko, Nomura Masahiro, Kujime Sae, Noda Yoshiko, Kondo Noriyasu, Nakaya Yutaka, Ito Susumu
Department of Digestive and Cardiovascular Medicine, University of Tokushima Graduate School, Tokushima, Japan.
Arzneimittelforschung. 2004;54(8):427-35. doi: 10.1055/s-0031-1296995.
Nizatidine (CAS 76963-41-2, Acinon), an H2 receptor antagonist, not only inhibits acid secretion but also improves gastrointestinal motility. However, autonomic nervous function has not been studied in detail using electrogastrography (EGG). In the present study, two protocols were adopted to study nizatidine's effects on cardiac autonomic function and gastric motility. Protocol I--Acute: "Group C-I": 10 healthy volunteers received a single oral dose of nizatidine 150 mg. Protocol II--Chronic: "Group DM without N": 15 patients with diabetes mellitus (DM) were observed prior to administration of nizatidine. "Group DM with N": The same 15 patients with DM received nizatidine 300 mg/day for more than 30 days. "Group C-II": This control group was composed of 15 healthy volunteers not receiving nizatidine. In all groups, EGGs were recorded before and after a meal, and autonomic nervous function and QT interval of ECG dispersions were simultaneously evaluated. In Group C-I, nizatidine significantly increased the peak power amplitude of 3 cycles/min (cpm) frequency, but did not significantly change the dominant frequency of the 3-cpm waves. In Group DM with N, nizatidine administration significantly increased the peak power amplitude from 2.4 cpm or a lower frequency (bradygastria) to 3 cpm. Prior to nizatidine administration but after eating a meal, the peak power amplitude on EGG was not increased in Group DM without N. In Group DM with N, however, the EGG peak power amplitude increased to levels similar to those of the healthy subjects (Group C-II). Neither the single nor the chronic administration of nizatidine significantly prolonged the QT interval or increased the QT dispersion. A spectral analysis of heart rate variability showed that nizatidine administration, whether acute or chronic, did not significantly change the indices of autonomic nervous activity. Nizatidine may promote gastric emptying by inhibiting acetylcholine esterase, thus increasing cholinergic activity, and by acting directly on gastric smooth muscle. The results indicate that because nizatidine increases gastric motility without exerting a negative influence on the autonomic nerves, it may be a useful drug in patients with diabetic neuropathy.
尼扎替丁（CAS 76963-41-2，阿克宁）是一种H2受体拮抗剂，不仅能抑制胃酸分泌，还能改善胃肠动力。然而，尚未使用胃电图（EGG）对自主神经功能进行详细研究。在本研究中，采用了两种方案来研究尼扎替丁对心脏自主神经功能和胃动力的影响。方案I——急性：“C-I组”：10名健康志愿者单次口服150毫克尼扎替丁。方案II——慢性：“无尼扎替丁的糖尿病组”：在给予尼扎替丁之前，观察15名糖尿病（DM）患者。“有尼扎替丁的糖尿病组”：同样的15名糖尿病患者接受300毫克/天的尼扎替丁治疗超过30天。“C-II组”：该对照组由15名未接受尼扎替丁的健康志愿者组成。在所有组中，在饭前和饭后记录EGG，并同时评估自主神经功能和心电图离散度的QT间期。在C-I组中，尼扎替丁显著增加了3次/分钟（cpm）频率的峰值功率幅度，但3-cpm波的主导频率没有显著变化。在有尼扎替丁的糖尿病组中，给予尼扎替丁显著增加了从2.4 cpm或更低频率（胃动过缓）到3 cpm的峰值功率幅度。在无尼扎替丁的糖尿病组中，在给予尼扎替丁之前但饭后，EGG上的峰值功率幅度没有增加。然而，在有尼扎替丁的糖尿病组中，EGG峰值功率幅度增加到与健康受试者（C-II组）相似的水平。尼扎替丁的单次或长期给药均未显著延长QT间期或增加QT离散度。心率变异性的频谱分析表明，无论急性还是慢性给予尼扎替丁，均未显著改变自主神经活动指标。尼扎替丁可能通过抑制乙酰胆碱酯酶来促进胃排空，从而增加胆碱能活性，并直接作用于胃平滑肌。结果表明，由于尼扎替丁增加胃动力而不对自主神经产生负面影响，它可能是糖尿病神经病变患者的一种有用药物。
