Coulson R, Moses A M
J Pharmacol Exp Ther. 1975 Sep;194(3):603-13.
Chlorpropamide inhibited by 35 to 65% the increase in the urinary excretion of adenosine 3',5'-monophosphate (cyclic AMP) following a large dose (250 U) of parathyroid hormone (PTH) in normal subjects and patients with hypoparathyroidism and pseudohypoparathyroidism. By contrast, in normal subjects, the response of urinary cyclic AMP excretion to smaller amounts of PTH (15 and 30 U) was not decreased by chlorpropamide. Chlorpropamide did not decrease the phosphaturic response to any dose of PTH. The probable explanation for the discrepant effects of chlorpropamide on urinary cyclic AMP and phosphate excretions is that phosphaturia results from a minimal elevation of cyclic AMP and that chlorpropamide does not decrease cyclic AMP production to such a low level. Chlorpropamide decreased the accumulation of renal cyclic AMP in response to PTH in the parathyroidectomized rat, suggesting that this may be the mechanism of action for this drug in decreasing the urinary excretion of cyclic AMP in response to PTH in man. Tolazamide, another sulfonylurea, did not inhibit the elevation of urinary cyclic AMP excretion after PTH. Therefore, the sulfonylurea part of the molecule is probably not involved in the inhibition produced by chlorpropamide.
在正常受试者、甲状旁腺功能减退症患者及假性甲状旁腺功能减退症患者中，氯磺丙脲可抑制大剂量（250单位）甲状旁腺激素（PTH）后尿中3',5'-单磷酸腺苷（环磷腺苷）排泄量增加35%至65%。相比之下，在正常受试者中，氯磺丙脲并未降低尿中环磷腺苷排泄量对较少量PTH（15和30单位）的反应。氯磺丙脲并未降低对任何剂量PTH的磷尿反应。氯磺丙脲对尿中环磷腺苷和磷酸盐排泄产生不同作用的可能解释是，磷尿是由环磷腺苷的最小升高引起的，且氯磺丙脲不会将环磷腺苷的产生降低到如此低的水平。氯磺丙脲可降低甲状旁腺切除大鼠中肾环磷腺苷对PTH的积累，提示这可能是该药物在人体中降低尿中环磷腺苷对PTH排泄反应的作用机制。另一种磺脲类药物甲苯磺丁脲并未抑制PTH后尿中环磷腺苷排泄量的升高。因此，分子中的磺脲部分可能与氯磺丙脲产生的抑制作用无关。
