Hyperglycemic, antihypertensive and antidiuretic properties of Go. 8288 and its comparison with diazoxide

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.