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 receptor agonist, and placebo, on circulating adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined over 24 h after dosing, in 26 healthy male subjects. ACTH was measured by immunoradiometric assay and cortisol by radioimmunoassay. 2. After sumatriptan all subjects displayed a normal diurnal rhythm for circulating ACTH and cortisol compared with placebo. 3. There was a reduction in the trough circulating ACTH concentration over 0-4 h which was 18% with 100 mg (P = 0.002), and 25% with 200 mg (P < 0.001). The 5 h, post-prandial, peak ACTH 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 nadir concentration of ACTH over the 24 h and the ACTH concentration 24 h after sumatriptan were not, however, significantly reduced. All results 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 < 0.001). The 5 h, post-prandial, peak cortisol concentration was reduced by 16% with 100 mg (P = 0.012) and by 15% with 200 mg (P = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)
Entwisle
S J
SJ
Glaxo Research and Development Ltd (Clinical Pharmacology Unit, Northwick Park Hospital, Harrow, Middlesex.
Fowler
P A
PA
Thomas
M
M
Eckland
D J
DJ
Lettis
S
S
York
M
M
Freedman
P S
PS
D000284:Administration, Oral; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000704:Analysis of Variance; D002940:Circadian Rhythm / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D015592:Immunoradiometric Assay; D008297:Male; D011863:Radioimmunoassay; D012984:Software; D018170:Sumatriptan / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D018170:Sumatriptan; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone