THE EFFECTS OF ORAL SUMATRIPTAN, A 5-HT1 RECEPTOR AGONIST, ON CIRCULATING ACTH AND CORTISOL CONCENTRATIONS IN MAN

1 The effects of oral sumatriptan (50, 100 and 200 mg), a 5-HT1 recept or agonist, and placebo, on circulating adrenocorticotrophic hormone ( ACTH) and cortisol concentrations were determined over 24 h after dosi ng, in 26 healthy male subjects. ACTH was measured by immunoradiometri c assay and cortisol by radioimmunoassay. 2 After sumatriptan all subj ects displayed a normal diurnal rhythm for circulating ACTH and cortis ol compared with placebo. 3 There was a reduction in the trough circul ating ACTH concentration over 0-4 h which was 18% with 100 mg (P = 0.0 02), and 25% with 200 mg (P < 0.001). The 5 h, post-prandial, peak ACT H concentration was reduced by 21% with 100 mg (P = 0.018) and by 20% with 200 mg (P = 0.024). The weighted mean ACTH over 24 h was reduced by 8% with 100 mg (P = 0.029) and by 8% with 200 mg (P = 0.018). The n adir concentration of ACTH over the 24 h and the ACTH concentration 24 h after sumatriptan were not, however, significantly reduced. All res ults are compared with placebo. 4 There was a reduction in the trough circulating cortisol concentration over 0-4 h which was 15% with 50 mg (P = 0.015), 14% with 100 mg (P = 0.022) and 24% with 200 mg (P < 0.0 01). The 5 h, post-prandial, peak cortisol concentration was reduced b y 16% with 100 mg (P = 0.012) and by 15% with 200 mg (P = 0.017). The weighted mean cortisol over 24 h was reduced by 9% with 50 mg (P = 0.0 20), 9% by 100 mg (P = 0.024) and 12% by 200 mg (P = 0.002). The nadir concentration of cortisol over the 24 h and the cortisol concentratio n 24 h after the administration of sumatriptan were not, however, sign ificantly reduced. All results are compared with placebo. 5 Sumatripta n did not inhibit the post-prandial peak in circulating concentrations of cortisol and ACTH, although there was a diminution of this peak fo llowing 100 mg and 200 mg relative to placebo. 6 There was no effect o f sumatriptan on circulating ACTH and cortisol concentrations by 11 h after dosing, compared with placebo. 7 Sumatriptan has a small effect on the circulating cortisol concentration in healthy volunteers which is caused by a reduction in circulating ACTH concentration. These chan ges in hormone concentrations are within the normal diurnal variation and are not clinically important, even at twice the recommended therap eutic dose of 100 mg.