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.
Bochicchio
D
D
Cattedra di Endocrinologia e Medicina Costituzionale, Università di Milano, Italia.
Ambrosi
B
B
Faglia
G
G
D000224:Addison Disease / Q000097:blood*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008139:Loperamide / Q000494:pharmacology*; D008236:Lypressin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology*; D011897:Random Allocation
D010880:Piperidines; D008236:Lypressin; D008139:Loperamide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone