佐兰替丁（SK&F 95282）是一种强效的、能穿透血脑屏障的选择性组胺H2受体拮抗剂。

Zolantidine (SK&F 95282) is a potent selective brain-penetrating histamine H2-receptor antagonist.

Calcutt C R, Ganellin C R, Griffiths R, Leigh B K, Maguire J P, Mitchell R C, Mylek M E, Parsons M E, Smith I R, Young R C

Smith Kline & French Research Limited, The Frythe, Welwyn, Hertfordshire.

Br J Pharmacol. 1988 Jan;93(1):69-78. doi: 10.1111/j.1476-5381.1988.tb11406.x.

Abstract

The novel benzthiazole derivative zolantidine (SK&F 95282) is a potent antagonist of histamine at H2-receptors in guinea-pig atrium and rat uterus. Only apparent pA2 values of 7.46 and 7.26 respectively could be calculated since the slopes of the Schild plots were significantly less than unity. 2. Zolantidine is equally potent as an antagonist at histamine H2-receptors in guinea-pig brain. The compound inhibited histamine stimulated adenylate cyclase (pKi 7.3) and dimaprit stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation (approx pA2 7.63), and competed with [3H]-tiotidine binding (pKi 7.17). 3. Zolantidine is at least 30 fold more potent at H2-receptors than at other peripheral and central receptors investigated. 4. Infusion of zolantidine into rats produces a brain concentration greater than the plateau blood concentration (brain/blood ratio 1.45). 5. Zolantidine is thus characterized as a potent selective brain-penetrating H2-receptor antagonist, and will be a valuable pharmacological tool for investigating possible physiological and pathological roles for histamine in the central nervous system.

摘要

新型苯并噻唑衍生物佐兰替丁（SK&F 95282）是豚鼠心房和大鼠子宫中组胺H2受体的强效拮抗剂。由于希尔德图的斜率明显小于1，因此只能分别计算出表观pA2值为7.46和7.26。2. 佐兰替丁作为豚鼠脑中组胺H2受体的拮抗剂效力相当。该化合物抑制组胺刺激的腺苷酸环化酶（pKi 7.3）和二甲普利刺激的3':5'-环磷酸腺苷（环磷酸腺苷）积累（约pA2 7.63），并与[3H] - 替丁定结合竞争（pKi 7.17）。3. 佐兰替丁在H2受体上的效力比所研究的其他外周和中枢受体至少强30倍。4. 向大鼠输注佐兰替丁会使脑浓度高于平稳期血药浓度（脑/血比为1.45）。5. 因此，佐兰替丁被表征为一种强效的选择性脑渗透性H2受体拮抗剂，并且将成为研究组胺在中枢神经系统中可能的生理和病理作用的有价值的药理学工具。