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J Pharmacol Exp Ther. 1984 Jan;228(1):168-73.

Mechanisms involved in the hyperglycemic response induced by clonidine and other alpha-2 adrenoceptor agonists.


Clonidine induced a dose-dependent hyperglycemic response in fed rats, a minimal hyperglycemic response in 48-hr fasted rats and had no effect on blood glucose in 16-hr fasted, streptozotocin-diabetic rats. At a dose of 0.1 mg/kg, there was an equivalent hyperglycemic response in fed rats whether clonidine was administered orally, i.v. or i.p. A hyperglycemic effect was also observed with the central and peripheral alpha-2 adrenoceptor agonist, guanabenz (0.1 mg/kg i.v.). In contrast, 2-(3-4-dihydroxyphenylimino) imidazoline, an alpha-2 agonist which does not penetrate into the central nervous system, caused a lowering of blood glucose at the same dose. The hyperglycemic response induced by clonidine was partially inhibited by the selective alpha-2 antagonists, yohimbine and rauwolscine, and the nonselective alpha antagonist, phentolamine. The hyperglycemic response induced by clonidine was not affected by the selective alpha-1 adrenoceptor antagonists, prazosin or corynanthine. Methoxamine, an alpha-1 agonist, had no effect on clonidine-induced hyperglycemia. The hyperglycemic response to clonidine was partially inhibited by 3-mercaptopicolinic acid, an inhibitor of gluconeogenesis, but was not affected by pretreatment with the H2-histamine receptor antagonist, metiamide, the prostaglandin syntheses inhibitor, idomethacin, or the beta adrenoceptor antagonist, propranolol. These results suggest that 1) the hyperglycemic response induced by clonidine and other alpha-2 adrenergic agonists is mediated by alpha-2 adrenergic receptors located within the central nervous system and 2) clonidine-induced hyperglycemia is effected, in part, by enhanced gluconeogenesis.

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