Central effects of DN1417, a novel TRH analog, on plasma glucose and catecholamines in conscious rats.

Intracerebroventricular (icv) injection of DN1417 (0.3, 3 and 30 nmol/rat), a TRH analog, resulted in a dose-related increase in plasma glucose, epinephrine and norepinephrine levels in conscious male rats. The effects of DN1417 were more potent and longer-lasting than those of TRH on a molar basis. Intravenous injection of DN1417 (30 nmol/rat) did not change plasma glucose, epinephrine and norepinephrine levels. Pretreatment with hexamethonium (1.5 mg/100 g body wt, iv, 2 min before) inhibited plasma glucose, epinephrine and norepinephrine responses to DN1417 (3 nmol/rat, icv). DN1417 did not change plasma glucose, epinephrine and norepinephrine levels in rats after total adrenalectomy. In the animals pretreated with cysteamine (30 mg/100 g body wt, sc, 4 h before), basal plasma glucose, epinephrine and norepinephrine levels were raised, and exaggerated responses of plasma glucose, epinephrine and norepinephrine to DN1417 (3 nmol/rat, icv) were obtained. These results indicate that DN1417 has a potent and long-lasting effect in the central nervous system in stimulating the secretion of catecholamines through the autonomic nervous system, which is associated with an elevation of plasma glucose and that endogenous hypothalamic somatostatin may inhibit the action of DN1417.