Kaul C L, Talwalker P K, Grewal R S
Arch Int Pharmacodyn Ther. 1978 May;233(1):92-106.
Hyperglycemic, antihypertensive and antidiuretic activities of Go.8288 and diazoxide were evaluated in the rat. Go.8288 and diazoxide induced hyperglycemia which was blocked by adrenalectomy and demedullation. Pretreatmnet with hydrocortisone completely restored the hyperglycemic effect of diazoxide but only partially that of Go.8288. The hyperglycemic effect of Go.8288 and diazoxide was antagonized by glibenclamide, whereas tolbutamide antagonized only diazoxide-induced hyperglycemia. Pretreatment with oxprenolol antagonized diazoxide-induced hyperglycemia but not that of Go.8288. Guanethidine antagonized the hyperglycemic effect of Go.8288 but not that of diazoxide. Go.8288 and diazoxide markedly inhibited insulin secretion in vivo. Unlike Go.8288, diazoxide further accentuated the hyperglycemic effect in the streptozotocin diabetic rat. Diazoxide significantly increased plasma FFA and plasma renin activity but Go.8288 had no effect. In the normotensive cats and dogs and renal hypertensive rats both compounds lowered arterial blood pressure. Unlike diazoxide, Go.8288 was active orally in normotensive dogs. Similar to diazoxide Go.8288 showed an antidiuretic effect in the rat. It is therefore concluded that despite some similarities, Go.8288 shows important differences in its biological profile from that of diazoxide.
在大鼠中评估了Go.8288和二氮嗪的升血糖、降压和抗利尿活性。Go.8288和二氮嗪均可诱导高血糖，而肾上腺切除术和去髓质术可阻断这种高血糖。用氢化可的松预处理可完全恢复二氮嗪的高血糖作用，但仅部分恢复Go.8288的高血糖作用。格列本脲可拮抗Go.8288和二氮嗪的高血糖作用，而甲苯磺丁脲仅拮抗二氮嗪诱导的高血糖。用氧烯洛尔预处理可拮抗二氮嗪诱导的高血糖，但不能拮抗Go.8288诱导的高血糖。胍乙啶可拮抗Go.8288的高血糖作用，但不能拮抗二氮嗪的高血糖作用。Go.8288和二氮嗪在体内均显著抑制胰岛素分泌。与Go.8288不同，二氮嗪可进一步加重链脲佐菌素糖尿病大鼠的高血糖作用。二氮嗪可显著升高血浆游离脂肪酸和血浆肾素活性，但Go.8288无此作用。在血压正常的猫和狗以及肾性高血压大鼠中，这两种化合物均可降低动脉血压。与二氮嗪不同，Go.8288对血压正常的狗口服有效。与二氮嗪相似，Go.8288在大鼠中显示出抗利尿作用。因此得出结论，尽管存在一些相似之处，但Go.8288在生物学特性上与二氮嗪存在重要差异。
