Zolmitriptan-induced growth hormone release in humans: mediation by 5-HT1D receptors?

Effective neuroendocrine probes of 5-HT1B and 5-HT1D receptor function may facilitate investigation of the role of these receptor subtypes in the pathophysiology of depression and the mode of action of antidepressant medication.

To investigate the neuroendocrine profile of the 5-HT1B/1D receptor agonist, zolmitriptan, in healthy volunteers.

Twelve subjects entered a double-blind, placebo-controlled, cross-over design study of zolmitriptan (5 mg orally). Blood samples were taken at 15-min intervals for assay of prolactin and growth hormone. A further six healthy men were recruited to an equivalent study to examine the effect of ketanserin (a 5-HT receptor antagonist with some preference for 5-HT1D over 5-HT1B receptors) on the growth hormone response to zolmitriptan.

Zolmitriptan significantly increased plasma growth hormone but had no effect on plasma prolactin or oral temperature. The increase in growth hormone produced by zolmitriptan was significantly attenuated by ketanserin.

We suggest that the ability of triptans such as zolmitriptan, sumatriptan and rizatriptan to increase plasma growth hormone is mediated by their common agonist activity at postsynaptic 5-HT1D receptors.