Loperamide, an opiate analog, differently modifies the adrenocorticotropin responses to corticotropin-releasing hormone and lysine vasopressin in patients with Addison's disease.
Loperamide is a peripheral opiate agonist able to inhibit ACTH secretion. In this work, the interactions between loperamide and two ACTH secretagogues, lysine vasopressin (LVP) and corticotropin-releasing hormone (CRH), were investigated in patients with Addison's disease. After loperamide (16 mg orally) or placebo administration, 5 patients received LVP (0.06 IU/kg i.v. over 1 h) and 6 patients received oCRH (1 micrograms/kg i.v. as bolus). In all patients loperamide induced a significant fall in plasma ACTH levels. LVP increased ACTH levels after both loperamide (from 48 +/- 17.3 to a peak of 95 +/- 21 pmol/l) and placebo (from 231 +/- 59.5 to 365 +/- 86.6 pmol/l): the interaction between treatments and time was not significant. CRH caused a rise in plasma ACTH after both loperamide (from 30 +/- 16.6 to a peak of 108 +/- 31 pmol/l) and placebo (from 98.5 +/- 47 to 211 +/- 61.7 pmol/l): the interaction between treatments and time was significant, and the first phase of CRH-induced ACTH secretion was significantly lower after loperamide. These data demonstrate that loperamide differently modifies the stimulatory action of LVP and CRH on ACTH secretion: namely, LVP and loperamide act in an additive manner, while CRH and loperamide interact in a non additive way. Although these findings might be explained by the involvement of different intracellular ACTH-secreting mechanisms, an influence of loperamide on some suprapituitary factors modulating the ACTH response is suggested.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y
Loperamide loperamide loperamide loperamide LVP LVP loperamide loperamide loperamide lysine vasopressin LVP loperamide LVP loperamide LVP loperamide loperamide Loperamide lysine vasopressin LVP CRH ACTH LVP CRH ACTH ACTH ACTH lysine vasopressin LVP corticotropin-releasing hormone CRH LVP oCRH ACTH LVP ACTH ACTH CRH ACTH CRH ACTH lysine vasopressin adrenocorticotropin corticotropin-releasing hormone