Künneke M, Lorenz W, Duda D, Künkel D, Schunack W
Institute of Theoretical Surgery, Centre of Operative Medicine I, Phillips-University Marburg, Germany.
Agents Actions. 1994 Jun;41 Spec No:C131-3. doi: 10.1007/BF02007798.
In a controlled clinical trial on histamine release in anaesthesia, it was suspected that the antihypertensive fixed-dose combination drug Betathiazid masked clinical signs of histamine release. By structure analysis of its constituents (propranolol, triamterene and hydrochlorothiazide), hydrochlorothiazide was considered to be most likely an H1-antagonist. An aqueous solution of the whole drug tablet (2 x 10(-4) M propranolol, 2.9 x 10(-5) M triamterene, 1.7 x 10(-5) M hydrochlorothiazide) and of the individual substances (1 microM each) was tested in the classical H1-receptor assay using the guinea pig ileum. Betathiazid in total suppressed the contraction to histamine (78% inhibition), but not to carbachol. Propranolol and triamterene had depressive effects (14% and 38% inhibition), but hydrochlorothiazide potentiated the contractions to histamine (75% potentiation). In all cases, the type of antagonism was not competitive. Although different mechanisms may account for the modulatory effects of Betathiazid, they have to be considered in the interpretation of clinical studies, especially for relating mediator concentrations with clinical signs.
在一项关于麻醉中组胺释放的对照临床试验中，有人怀疑抗高血压固定剂量复方药物倍他噻嗪掩盖了组胺释放的临床体征。通过对其成分（普萘洛尔、氨苯蝶啶和氢氯噻嗪）进行结构分析，认为氢氯噻嗪很可能是一种H1拮抗剂。使用豚鼠回肠，在经典的H1受体试验中对整片药物片剂的水溶液（2×10⁻⁴ M普萘洛尔、2.9×10⁻⁵ M氨苯蝶啶、1.7×10⁻⁵ M氢氯噻嗪）以及各单一物质（每种1 μM）进行了测试。倍他噻嗪总体上抑制了对组胺的收缩反应（抑制率78%），但对卡巴胆碱的收缩反应无抑制作用。普萘洛尔和氨苯蝶啶有抑制作用（抑制率分别为14%和38%），但氢氯噻嗪增强了对组胺的收缩反应（增强率75%）。在所有情况下，拮抗类型均非竞争性。尽管可能有不同机制解释倍他噻嗪的调节作用，但在解释临床研究时必须予以考虑，尤其是在将介质浓度与临床体征相关联时。
